InterMEL: An international biorepository and clinical database to uncover predictors of survival in early-stage melanoma.

<h4<Introduction</h4<We are conducting a multicenter study to identify classifiers predictive of disease-specific survival in patients with primary melanomas. Here we delineate the unique aspects, challenges, and best practices for optimizing a study of generally small-sized pigmented tumor samples including primary melanomas of at least 1.05mm from AJTCC TNM stage IIA-IIID patients. We also evaluated tissue-derived predictors of extracted nucleic acids' quality and success in downstream testing. This ongoing study will target 1,000 melanomas within the international InterMEL consortium.<h4<Methods</h4<Following a pre-established protocol, participating centers ship formalin-fixed paraffin embedded (FFPE) tissue sections to Memorial Sloan Kettering Cancer Center for the centralized handling, dermatopathology review and histology-guided coextraction of RNA and DNA. Samples are distributed for evaluation of somatic mutations using next gen sequencing (NGS) with the MSK-IMPACTTM assay, methylation-profiling (Infinium MethylationEPIC arrays), and miRNA expression (Nanostring nCounter Human v3 miRNA Expression Assay).<h4<Results</h4<Sufficient material was obtained for screening of miRNA expression in 683/685 (99%) eligible melanomas, methylation in 467 (68%), and somatic mutations in 560 (82%). In 446/685 (65%) cases, aliquots of RNA/DNA were sufficient for testing with all three platforms. Among samples evaluated by the time of this analysis, the mean NGS coverage was 249x, 59 (18.6%) samples had coverage below 100x, and 41/414 (10%) failed methylation QC due to low intensity probes or insufficient Meta-Mixed Interquartile (BMIQ)- and single sample (ss)- Noob normalizations. Six of 683 RNAs (1%) failed Nanostring QC due to the low proportion of probes above the minimum threshold. Age of the FFPE tissue blocks (p<0.001) and time elapsed from sectioning to co-extraction (p = 0.002) were associated with methylation screening failures. Melanin reduced the ability to amplify fragments of 200bp or greater (absent/lightly pigmented vs heavily pigmented, p<0.003). Conversely, heavily pigmented tumors rendered greater amounts of RNA (p<0.001), and of RNA above 200 nucleotides (p<0.001).<h4<Conclusion</h4<Our experience with many archival tissues demonstrates that with careful management of tissue processing and quality control it is possible to conduct multi-omic studies in a complex multi-institutional setting for investigations involving minute quantities of FFPE tumors, as in studies of early-stage melanoma. The study describes, for the first time, the optimal strategy for obtaining archival and limited tumor tissue, the characteristics of the nucleic acids co-extracted from a unique cell lysate, and success rate in downstream applications. In addition, our findings provide an estimate of the anticipated attrition that will guide other large multicenter research and consortia. Ausführliche Beschreibung

Gespeichert in:

Autor*in:	Irene Orlow [verfasserIn] Keimya D Sadeghi [verfasserIn] Sharon N Edmiston [verfasserIn] Jessica M Kenney [verfasserIn] Cecilia Lezcano [verfasserIn] James S Wilmott [verfasserIn] Anne E Cust [verfasserIn] Richard A Scolyer [verfasserIn] Graham J Mann [verfasserIn] Tim K Lee [verfasserIn] Hazel Burke [verfasserIn] Valerie Jakrot [verfasserIn] Ping Shang [verfasserIn] Peter M Ferguson [verfasserIn] Tawny W Boyce [verfasserIn] Jennifer S Ko [verfasserIn] Peter Ngo [verfasserIn] Pauline Funchain [verfasserIn] Judy R Rees [verfasserIn] Kelli O'Connell [verfasserIn] Honglin Hao [verfasserIn] Eloise Parrish [verfasserIn] Kathleen Conway [verfasserIn] Paul B Googe [verfasserIn] David W Ollila [verfasserIn] Stergios J Moschos [verfasserIn] Eva Hernando [verfasserIn] Douglas Hanniford [verfasserIn] Diana Argibay [verfasserIn] Christopher I Amos [verfasserIn] Jeffrey E Lee [verfasserIn] Iman Osman [verfasserIn] Li Luo [verfasserIn] Pei-Fen Kuan [verfasserIn] Arshi Aurora [verfasserIn] Bonnie E Gould Rothberg [verfasserIn] Marcus W Bosenberg [verfasserIn] Meg R Gerstenblith [verfasserIn] Cheryl Thompson [verfasserIn] Paul N Bogner [verfasserIn] Ivan P Gorlov [verfasserIn] Sheri L Holmen [verfasserIn] Elise K Brunsgaard [verfasserIn] Yvonne M Saenger [verfasserIn] Ronglai Shen [verfasserIn] Venkatraman Seshan [verfasserIn] Eduardo Nagore [verfasserIn] Marc S Ernstoff [verfasserIn] Klaus J Busam [verfasserIn] Colin B Begg [verfasserIn] Nancy E Thomas [verfasserIn] Marianne Berwick [verfasserIn] InterMEL Consortium [verfasserIn]

Format:	E-Artikel
Sprache:	Englisch

Erschienen:	2023

Übergeordnetes Werk:	In: PLoS ONE - Public Library of Science (PLoS), 2007, 18(2023), 4, p e0269324
Übergeordnetes Werk:	volume:18 ; year:2023 ; number:4, p e0269324

Links:	Link aufrufen Link aufrufen Link aufrufen Journal toc

DOI / URN:	10.1371/journal.pone.0269324

Katalog-ID:	DOAJ089056396

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520			\|a <h4<Introduction</h4<We are conducting a multicenter study to identify classifiers predictive of disease-specific survival in patients with primary melanomas. Here we delineate the unique aspects, challenges, and best practices for optimizing a study of generally small-sized pigmented tumor samples including primary melanomas of at least 1.05mm from AJTCC TNM stage IIA-IIID patients. We also evaluated tissue-derived predictors of extracted nucleic acids' quality and success in downstream testing. This ongoing study will target 1,000 melanomas within the international InterMEL consortium.<h4<Methods</h4<Following a pre-established protocol, participating centers ship formalin-fixed paraffin embedded (FFPE) tissue sections to Memorial Sloan Kettering Cancer Center for the centralized handling, dermatopathology review and histology-guided coextraction of RNA and DNA. Samples are distributed for evaluation of somatic mutations using next gen sequencing (NGS) with the MSK-IMPACTTM assay, methylation-profiling (Infinium MethylationEPIC arrays), and miRNA expression (Nanostring nCounter Human v3 miRNA Expression Assay).<h4<Results</h4<Sufficient material was obtained for screening of miRNA expression in 683/685 (99%) eligible melanomas, methylation in 467 (68%), and somatic mutations in 560 (82%). In 446/685 (65%) cases, aliquots of RNA/DNA were sufficient for testing with all three platforms. Among samples evaluated by the time of this analysis, the mean NGS coverage was 249x, 59 (18.6%) samples had coverage below 100x, and 41/414 (10%) failed methylation QC due to low intensity probes or insufficient Meta-Mixed Interquartile (BMIQ)- and single sample (ss)- Noob normalizations. Six of 683 RNAs (1%) failed Nanostring QC due to the low proportion of probes above the minimum threshold. Age of the FFPE tissue blocks (p<0.001) and time elapsed from sectioning to co-extraction (p = 0.002) were associated with methylation screening failures. Melanin reduced the ability to amplify fragments of 200bp or greater (absent/lightly pigmented vs heavily pigmented, p<0.003). Conversely, heavily pigmented tumors rendered greater amounts of RNA (p<0.001), and of RNA above 200 nucleotides (p<0.001).<h4<Conclusion</h4<Our experience with many archival tissues demonstrates that with careful management of tissue processing and quality control it is possible to conduct multi-omic studies in a complex multi-institutional setting for investigations involving minute quantities of FFPE tumors, as in studies of early-stage melanoma. The study describes, for the first time, the optimal strategy for obtaining archival and limited tumor tissue, the characteristics of the nucleic acids co-extracted from a unique cell lysate, and success rate in downstream applications. In addition, our findings provide an estimate of the anticipated attrition that will guide other large multicenter research and consortia.
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700	0		\|a Keimya D Sadeghi \|e verfasserin \|4 aut
700	0		\|a Sharon N Edmiston \|e verfasserin \|4 aut
700	0		\|a Jessica M Kenney \|e verfasserin \|4 aut
700	0		\|a Cecilia Lezcano \|e verfasserin \|4 aut
700	0		\|a James S Wilmott \|e verfasserin \|4 aut
700	0		\|a Anne E Cust \|e verfasserin \|4 aut
700	0		\|a Richard A Scolyer \|e verfasserin \|4 aut
700	0		\|a Graham J Mann \|e verfasserin \|4 aut
700	0		\|a Tim K Lee \|e verfasserin \|4 aut
700	0		\|a Hazel Burke \|e verfasserin \|4 aut
700	0		\|a Valerie Jakrot \|e verfasserin \|4 aut
700	0		\|a Ping Shang \|e verfasserin \|4 aut
700	0		\|a Peter M Ferguson \|e verfasserin \|4 aut
700	0		\|a Tawny W Boyce \|e verfasserin \|4 aut
700	0		\|a Jennifer S Ko \|e verfasserin \|4 aut
700	0		\|a Peter Ngo \|e verfasserin \|4 aut
700	0		\|a Pauline Funchain \|e verfasserin \|4 aut
700	0		\|a Judy R Rees \|e verfasserin \|4 aut
700	0		\|a Kelli O'Connell \|e verfasserin \|4 aut
700	0		\|a Honglin Hao \|e verfasserin \|4 aut
700	0		\|a Eloise Parrish \|e verfasserin \|4 aut
700	0		\|a Kathleen Conway \|e verfasserin \|4 aut
700	0		\|a Paul B Googe \|e verfasserin \|4 aut
700	0		\|a David W Ollila \|e verfasserin \|4 aut
700	0		\|a Stergios J Moschos \|e verfasserin \|4 aut
700	0		\|a Eva Hernando \|e verfasserin \|4 aut
700	0		\|a Douglas Hanniford \|e verfasserin \|4 aut
700	0		\|a Diana Argibay \|e verfasserin \|4 aut
700	0		\|a Christopher I Amos \|e verfasserin \|4 aut
700	0		\|a Jeffrey E Lee \|e verfasserin \|4 aut
700	0		\|a Iman Osman \|e verfasserin \|4 aut
700	0		\|a Li Luo \|e verfasserin \|4 aut
700	0		\|a Pei-Fen Kuan \|e verfasserin \|4 aut
700	0		\|a Arshi Aurora \|e verfasserin \|4 aut
700	0		\|a Bonnie E Gould Rothberg \|e verfasserin \|4 aut
700	0		\|a Marcus W Bosenberg \|e verfasserin \|4 aut
700	0		\|a Meg R Gerstenblith \|e verfasserin \|4 aut
700	0		\|a Cheryl Thompson \|e verfasserin \|4 aut
700	0		\|a Paul N Bogner \|e verfasserin \|4 aut
700	0		\|a Ivan P Gorlov \|e verfasserin \|4 aut
700	0		\|a Sheri L Holmen \|e verfasserin \|4 aut
700	0		\|a Elise K Brunsgaard \|e verfasserin \|4 aut
700	0		\|a Yvonne M Saenger \|e verfasserin \|4 aut
700	0		\|a Ronglai Shen \|e verfasserin \|4 aut
700	0		\|a Venkatraman Seshan \|e verfasserin \|4 aut
700	0		\|a Eduardo Nagore \|e verfasserin \|4 aut
700	0		\|a Marc S Ernstoff \|e verfasserin \|4 aut
700	0		\|a Klaus J Busam \|e verfasserin \|4 aut
700	0		\|a Colin B Begg \|e verfasserin \|4 aut
700	0		\|a Nancy E Thomas \|e verfasserin \|4 aut
700	0		\|a Marianne Berwick \|e verfasserin \|4 aut
700	0		\|a InterMEL Consortium \|e verfasserin \|4 aut
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allfields	10.1371/journal.pone.0269324 doi (DE-627)DOAJ089056396 (DE-599)DOAJ2122630446b94345873b74cdda1850a8 DE-627 ger DE-627 rakwb eng Irene Orlow verfasserin aut InterMEL: An international biorepository and clinical database to uncover predictors of survival in early-stage melanoma. 2023 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier <h4<Introduction</h4<We are conducting a multicenter study to identify classifiers predictive of disease-specific survival in patients with primary melanomas. Here we delineate the unique aspects, challenges, and best practices for optimizing a study of generally small-sized pigmented tumor samples including primary melanomas of at least 1.05mm from AJTCC TNM stage IIA-IIID patients. We also evaluated tissue-derived predictors of extracted nucleic acids' quality and success in downstream testing. This ongoing study will target 1,000 melanomas within the international InterMEL consortium.<h4<Methods</h4<Following a pre-established protocol, participating centers ship formalin-fixed paraffin embedded (FFPE) tissue sections to Memorial Sloan Kettering Cancer Center for the centralized handling, dermatopathology review and histology-guided coextraction of RNA and DNA. Samples are distributed for evaluation of somatic mutations using next gen sequencing (NGS) with the MSK-IMPACTTM assay, methylation-profiling (Infinium MethylationEPIC arrays), and miRNA expression (Nanostring nCounter Human v3 miRNA Expression Assay).<h4<Results</h4<Sufficient material was obtained for screening of miRNA expression in 683/685 (99%) eligible melanomas, methylation in 467 (68%), and somatic mutations in 560 (82%). In 446/685 (65%) cases, aliquots of RNA/DNA were sufficient for testing with all three platforms. Among samples evaluated by the time of this analysis, the mean NGS coverage was 249x, 59 (18.6%) samples had coverage below 100x, and 41/414 (10%) failed methylation QC due to low intensity probes or insufficient Meta-Mixed Interquartile (BMIQ)- and single sample (ss)- Noob normalizations. Six of 683 RNAs (1%) failed Nanostring QC due to the low proportion of probes above the minimum threshold. Age of the FFPE tissue blocks (p<0.001) and time elapsed from sectioning to co-extraction (p = 0.002) were associated with methylation screening failures. Melanin reduced the ability to amplify fragments of 200bp or greater (absent/lightly pigmented vs heavily pigmented, p<0.003). Conversely, heavily pigmented tumors rendered greater amounts of RNA (p<0.001), and of RNA above 200 nucleotides (p<0.001).<h4<Conclusion</h4<Our experience with many archival tissues demonstrates that with careful management of tissue processing and quality control it is possible to conduct multi-omic studies in a complex multi-institutional setting for investigations involving minute quantities of FFPE tumors, as in studies of early-stage melanoma. The study describes, for the first time, the optimal strategy for obtaining archival and limited tumor tissue, the characteristics of the nucleic acids co-extracted from a unique cell lysate, and success rate in downstream applications. In addition, our findings provide an estimate of the anticipated attrition that will guide other large multicenter research and consortia. Medicine R Science Q Keimya D Sadeghi verfasserin aut Sharon N Edmiston verfasserin aut Jessica M Kenney verfasserin aut Cecilia Lezcano verfasserin aut James S Wilmott verfasserin aut Anne E Cust verfasserin aut Richard A Scolyer verfasserin aut Graham J Mann verfasserin aut Tim K Lee verfasserin aut Hazel Burke verfasserin aut Valerie Jakrot verfasserin aut Ping Shang verfasserin aut Peter M Ferguson verfasserin aut Tawny W Boyce verfasserin aut Jennifer S Ko verfasserin aut Peter Ngo verfasserin aut Pauline Funchain verfasserin aut Judy R Rees verfasserin aut Kelli O'Connell verfasserin aut Honglin Hao verfasserin aut Eloise Parrish verfasserin aut Kathleen Conway verfasserin aut Paul B Googe verfasserin aut David W Ollila verfasserin aut Stergios J Moschos verfasserin aut Eva Hernando verfasserin aut Douglas Hanniford verfasserin aut Diana Argibay verfasserin aut Christopher I Amos verfasserin aut Jeffrey E Lee verfasserin aut Iman Osman verfasserin aut Li Luo verfasserin aut Pei-Fen Kuan verfasserin aut Arshi Aurora verfasserin aut Bonnie E Gould Rothberg verfasserin aut Marcus W Bosenberg verfasserin aut Meg R Gerstenblith verfasserin aut Cheryl Thompson verfasserin aut Paul N Bogner verfasserin aut Ivan P Gorlov verfasserin aut Sheri L Holmen verfasserin aut Elise K Brunsgaard verfasserin aut Yvonne M Saenger verfasserin aut Ronglai Shen verfasserin aut Venkatraman Seshan verfasserin aut Eduardo Nagore verfasserin aut Marc S Ernstoff verfasserin aut Klaus J Busam verfasserin aut Colin B Begg verfasserin aut Nancy E Thomas verfasserin aut Marianne Berwick verfasserin aut InterMEL Consortium verfasserin aut In PLoS ONE Public Library of Science (PLoS), 2007 18(2023), 4, p e0269324 (DE-627)523574592 (DE-600)2267670-3 19326203 nnns volume:18 year:2023 number:4, p e0269324 https://doi.org/10.1371/journal.pone.0269324 kostenfrei https://doaj.org/article/2122630446b94345873b74cdda1850a8 kostenfrei https://doi.org/10.1371/journal.pone.0269324 kostenfrei https://doaj.org/toc/1932-6203 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_34 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_206 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_235 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2031 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2061 GBV_ILN_2111 GBV_ILN_2113 GBV_ILN_2190 GBV_ILN_2522 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4335 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 18 2023 4, p e0269324
spelling	10.1371/journal.pone.0269324 doi (DE-627)DOAJ089056396 (DE-599)DOAJ2122630446b94345873b74cdda1850a8 DE-627 ger DE-627 rakwb eng Irene Orlow verfasserin aut InterMEL: An international biorepository and clinical database to uncover predictors of survival in early-stage melanoma. 2023 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier <h4<Introduction</h4<We are conducting a multicenter study to identify classifiers predictive of disease-specific survival in patients with primary melanomas. Here we delineate the unique aspects, challenges, and best practices for optimizing a study of generally small-sized pigmented tumor samples including primary melanomas of at least 1.05mm from AJTCC TNM stage IIA-IIID patients. We also evaluated tissue-derived predictors of extracted nucleic acids' quality and success in downstream testing. This ongoing study will target 1,000 melanomas within the international InterMEL consortium.<h4<Methods</h4<Following a pre-established protocol, participating centers ship formalin-fixed paraffin embedded (FFPE) tissue sections to Memorial Sloan Kettering Cancer Center for the centralized handling, dermatopathology review and histology-guided coextraction of RNA and DNA. Samples are distributed for evaluation of somatic mutations using next gen sequencing (NGS) with the MSK-IMPACTTM assay, methylation-profiling (Infinium MethylationEPIC arrays), and miRNA expression (Nanostring nCounter Human v3 miRNA Expression Assay).<h4<Results</h4<Sufficient material was obtained for screening of miRNA expression in 683/685 (99%) eligible melanomas, methylation in 467 (68%), and somatic mutations in 560 (82%). In 446/685 (65%) cases, aliquots of RNA/DNA were sufficient for testing with all three platforms. Among samples evaluated by the time of this analysis, the mean NGS coverage was 249x, 59 (18.6%) samples had coverage below 100x, and 41/414 (10%) failed methylation QC due to low intensity probes or insufficient Meta-Mixed Interquartile (BMIQ)- and single sample (ss)- Noob normalizations. Six of 683 RNAs (1%) failed Nanostring QC due to the low proportion of probes above the minimum threshold. Age of the FFPE tissue blocks (p<0.001) and time elapsed from sectioning to co-extraction (p = 0.002) were associated with methylation screening failures. Melanin reduced the ability to amplify fragments of 200bp or greater (absent/lightly pigmented vs heavily pigmented, p<0.003). Conversely, heavily pigmented tumors rendered greater amounts of RNA (p<0.001), and of RNA above 200 nucleotides (p<0.001).<h4<Conclusion</h4<Our experience with many archival tissues demonstrates that with careful management of tissue processing and quality control it is possible to conduct multi-omic studies in a complex multi-institutional setting for investigations involving minute quantities of FFPE tumors, as in studies of early-stage melanoma. The study describes, for the first time, the optimal strategy for obtaining archival and limited tumor tissue, the characteristics of the nucleic acids co-extracted from a unique cell lysate, and success rate in downstream applications. In addition, our findings provide an estimate of the anticipated attrition that will guide other large multicenter research and consortia. Medicine R Science Q Keimya D Sadeghi verfasserin aut Sharon N Edmiston verfasserin aut Jessica M Kenney verfasserin aut Cecilia Lezcano verfasserin aut James S Wilmott verfasserin aut Anne E Cust verfasserin aut Richard A Scolyer verfasserin aut Graham J Mann verfasserin aut Tim K Lee verfasserin aut Hazel Burke verfasserin aut Valerie Jakrot verfasserin aut Ping Shang verfasserin aut Peter M Ferguson verfasserin aut Tawny W Boyce verfasserin aut Jennifer S Ko verfasserin aut Peter Ngo verfasserin aut Pauline Funchain verfasserin aut Judy R Rees verfasserin aut Kelli O'Connell verfasserin aut Honglin Hao verfasserin aut Eloise Parrish verfasserin aut Kathleen Conway verfasserin aut Paul B Googe verfasserin aut David W Ollila verfasserin aut Stergios J Moschos verfasserin aut Eva Hernando verfasserin aut Douglas Hanniford verfasserin aut Diana Argibay verfasserin aut Christopher I Amos verfasserin aut Jeffrey E Lee verfasserin aut Iman Osman verfasserin aut Li Luo verfasserin aut Pei-Fen Kuan verfasserin aut Arshi Aurora verfasserin aut Bonnie E Gould Rothberg verfasserin aut Marcus W Bosenberg verfasserin aut Meg R Gerstenblith verfasserin aut Cheryl Thompson verfasserin aut Paul N Bogner verfasserin aut Ivan P Gorlov verfasserin aut Sheri L Holmen verfasserin aut Elise K Brunsgaard verfasserin aut Yvonne M Saenger verfasserin aut Ronglai Shen verfasserin aut Venkatraman Seshan verfasserin aut Eduardo Nagore verfasserin aut Marc S Ernstoff verfasserin aut Klaus J Busam verfasserin aut Colin B Begg verfasserin aut Nancy E Thomas verfasserin aut Marianne Berwick verfasserin aut InterMEL Consortium verfasserin aut In PLoS ONE Public Library of Science (PLoS), 2007 18(2023), 4, p e0269324 (DE-627)523574592 (DE-600)2267670-3 19326203 nnns volume:18 year:2023 number:4, p e0269324 https://doi.org/10.1371/journal.pone.0269324 kostenfrei https://doaj.org/article/2122630446b94345873b74cdda1850a8 kostenfrei https://doi.org/10.1371/journal.pone.0269324 kostenfrei https://doaj.org/toc/1932-6203 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_34 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_206 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_235 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2031 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2061 GBV_ILN_2111 GBV_ILN_2113 GBV_ILN_2190 GBV_ILN_2522 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4335 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 18 2023 4, p e0269324
allfields_unstemmed	10.1371/journal.pone.0269324 doi (DE-627)DOAJ089056396 (DE-599)DOAJ2122630446b94345873b74cdda1850a8 DE-627 ger DE-627 rakwb eng Irene Orlow verfasserin aut InterMEL: An international biorepository and clinical database to uncover predictors of survival in early-stage melanoma. 2023 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier <h4<Introduction</h4<We are conducting a multicenter study to identify classifiers predictive of disease-specific survival in patients with primary melanomas. Here we delineate the unique aspects, challenges, and best practices for optimizing a study of generally small-sized pigmented tumor samples including primary melanomas of at least 1.05mm from AJTCC TNM stage IIA-IIID patients. We also evaluated tissue-derived predictors of extracted nucleic acids' quality and success in downstream testing. This ongoing study will target 1,000 melanomas within the international InterMEL consortium.<h4<Methods</h4<Following a pre-established protocol, participating centers ship formalin-fixed paraffin embedded (FFPE) tissue sections to Memorial Sloan Kettering Cancer Center for the centralized handling, dermatopathology review and histology-guided coextraction of RNA and DNA. Samples are distributed for evaluation of somatic mutations using next gen sequencing (NGS) with the MSK-IMPACTTM assay, methylation-profiling (Infinium MethylationEPIC arrays), and miRNA expression (Nanostring nCounter Human v3 miRNA Expression Assay).<h4<Results</h4<Sufficient material was obtained for screening of miRNA expression in 683/685 (99%) eligible melanomas, methylation in 467 (68%), and somatic mutations in 560 (82%). In 446/685 (65%) cases, aliquots of RNA/DNA were sufficient for testing with all three platforms. Among samples evaluated by the time of this analysis, the mean NGS coverage was 249x, 59 (18.6%) samples had coverage below 100x, and 41/414 (10%) failed methylation QC due to low intensity probes or insufficient Meta-Mixed Interquartile (BMIQ)- and single sample (ss)- Noob normalizations. Six of 683 RNAs (1%) failed Nanostring QC due to the low proportion of probes above the minimum threshold. Age of the FFPE tissue blocks (p<0.001) and time elapsed from sectioning to co-extraction (p = 0.002) were associated with methylation screening failures. Melanin reduced the ability to amplify fragments of 200bp or greater (absent/lightly pigmented vs heavily pigmented, p<0.003). Conversely, heavily pigmented tumors rendered greater amounts of RNA (p<0.001), and of RNA above 200 nucleotides (p<0.001).<h4<Conclusion</h4<Our experience with many archival tissues demonstrates that with careful management of tissue processing and quality control it is possible to conduct multi-omic studies in a complex multi-institutional setting for investigations involving minute quantities of FFPE tumors, as in studies of early-stage melanoma. The study describes, for the first time, the optimal strategy for obtaining archival and limited tumor tissue, the characteristics of the nucleic acids co-extracted from a unique cell lysate, and success rate in downstream applications. In addition, our findings provide an estimate of the anticipated attrition that will guide other large multicenter research and consortia. Medicine R Science Q Keimya D Sadeghi verfasserin aut Sharon N Edmiston verfasserin aut Jessica M Kenney verfasserin aut Cecilia Lezcano verfasserin aut James S Wilmott verfasserin aut Anne E Cust verfasserin aut Richard A Scolyer verfasserin aut Graham J Mann verfasserin aut Tim K Lee verfasserin aut Hazel Burke verfasserin aut Valerie Jakrot verfasserin aut Ping Shang verfasserin aut Peter M Ferguson verfasserin aut Tawny W Boyce verfasserin aut Jennifer S Ko verfasserin aut Peter Ngo verfasserin aut Pauline Funchain verfasserin aut Judy R Rees verfasserin aut Kelli O'Connell verfasserin aut Honglin Hao verfasserin aut Eloise Parrish verfasserin aut Kathleen Conway verfasserin aut Paul B Googe verfasserin aut David W Ollila verfasserin aut Stergios J Moschos verfasserin aut Eva Hernando verfasserin aut Douglas Hanniford verfasserin aut Diana Argibay verfasserin aut Christopher I Amos verfasserin aut Jeffrey E Lee verfasserin aut Iman Osman verfasserin aut Li Luo verfasserin aut Pei-Fen Kuan verfasserin aut Arshi Aurora verfasserin aut Bonnie E Gould Rothberg verfasserin aut Marcus W Bosenberg verfasserin aut Meg R Gerstenblith verfasserin aut Cheryl Thompson verfasserin aut Paul N Bogner verfasserin aut Ivan P Gorlov verfasserin aut Sheri L Holmen verfasserin aut Elise K Brunsgaard verfasserin aut Yvonne M Saenger verfasserin aut Ronglai Shen verfasserin aut Venkatraman Seshan verfasserin aut Eduardo Nagore verfasserin aut Marc S Ernstoff verfasserin aut Klaus J Busam verfasserin aut Colin B Begg verfasserin aut Nancy E Thomas verfasserin aut Marianne Berwick verfasserin aut InterMEL Consortium verfasserin aut In PLoS ONE Public Library of Science (PLoS), 2007 18(2023), 4, p e0269324 (DE-627)523574592 (DE-600)2267670-3 19326203 nnns volume:18 year:2023 number:4, p e0269324 https://doi.org/10.1371/journal.pone.0269324 kostenfrei https://doaj.org/article/2122630446b94345873b74cdda1850a8 kostenfrei https://doi.org/10.1371/journal.pone.0269324 kostenfrei https://doaj.org/toc/1932-6203 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_34 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_206 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_235 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2031 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2061 GBV_ILN_2111 GBV_ILN_2113 GBV_ILN_2190 GBV_ILN_2522 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4335 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 18 2023 4, p e0269324
allfieldsGer	10.1371/journal.pone.0269324 doi (DE-627)DOAJ089056396 (DE-599)DOAJ2122630446b94345873b74cdda1850a8 DE-627 ger DE-627 rakwb eng Irene Orlow verfasserin aut InterMEL: An international biorepository and clinical database to uncover predictors of survival in early-stage melanoma. 2023 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier <h4<Introduction</h4<We are conducting a multicenter study to identify classifiers predictive of disease-specific survival in patients with primary melanomas. Here we delineate the unique aspects, challenges, and best practices for optimizing a study of generally small-sized pigmented tumor samples including primary melanomas of at least 1.05mm from AJTCC TNM stage IIA-IIID patients. We also evaluated tissue-derived predictors of extracted nucleic acids' quality and success in downstream testing. This ongoing study will target 1,000 melanomas within the international InterMEL consortium.<h4<Methods</h4<Following a pre-established protocol, participating centers ship formalin-fixed paraffin embedded (FFPE) tissue sections to Memorial Sloan Kettering Cancer Center for the centralized handling, dermatopathology review and histology-guided coextraction of RNA and DNA. Samples are distributed for evaluation of somatic mutations using next gen sequencing (NGS) with the MSK-IMPACTTM assay, methylation-profiling (Infinium MethylationEPIC arrays), and miRNA expression (Nanostring nCounter Human v3 miRNA Expression Assay).<h4<Results</h4<Sufficient material was obtained for screening of miRNA expression in 683/685 (99%) eligible melanomas, methylation in 467 (68%), and somatic mutations in 560 (82%). In 446/685 (65%) cases, aliquots of RNA/DNA were sufficient for testing with all three platforms. Among samples evaluated by the time of this analysis, the mean NGS coverage was 249x, 59 (18.6%) samples had coverage below 100x, and 41/414 (10%) failed methylation QC due to low intensity probes or insufficient Meta-Mixed Interquartile (BMIQ)- and single sample (ss)- Noob normalizations. Six of 683 RNAs (1%) failed Nanostring QC due to the low proportion of probes above the minimum threshold. Age of the FFPE tissue blocks (p<0.001) and time elapsed from sectioning to co-extraction (p = 0.002) were associated with methylation screening failures. Melanin reduced the ability to amplify fragments of 200bp or greater (absent/lightly pigmented vs heavily pigmented, p<0.003). Conversely, heavily pigmented tumors rendered greater amounts of RNA (p<0.001), and of RNA above 200 nucleotides (p<0.001).<h4<Conclusion</h4<Our experience with many archival tissues demonstrates that with careful management of tissue processing and quality control it is possible to conduct multi-omic studies in a complex multi-institutional setting for investigations involving minute quantities of FFPE tumors, as in studies of early-stage melanoma. The study describes, for the first time, the optimal strategy for obtaining archival and limited tumor tissue, the characteristics of the nucleic acids co-extracted from a unique cell lysate, and success rate in downstream applications. In addition, our findings provide an estimate of the anticipated attrition that will guide other large multicenter research and consortia. Medicine R Science Q Keimya D Sadeghi verfasserin aut Sharon N Edmiston verfasserin aut Jessica M Kenney verfasserin aut Cecilia Lezcano verfasserin aut James S Wilmott verfasserin aut Anne E Cust verfasserin aut Richard A Scolyer verfasserin aut Graham J Mann verfasserin aut Tim K Lee verfasserin aut Hazel Burke verfasserin aut Valerie Jakrot verfasserin aut Ping Shang verfasserin aut Peter M Ferguson verfasserin aut Tawny W Boyce verfasserin aut Jennifer S Ko verfasserin aut Peter Ngo verfasserin aut Pauline Funchain verfasserin aut Judy R Rees verfasserin aut Kelli O'Connell verfasserin aut Honglin Hao verfasserin aut Eloise Parrish verfasserin aut Kathleen Conway verfasserin aut Paul B Googe verfasserin aut David W Ollila verfasserin aut Stergios J Moschos verfasserin aut Eva Hernando verfasserin aut Douglas Hanniford verfasserin aut Diana Argibay verfasserin aut Christopher I Amos verfasserin aut Jeffrey E Lee verfasserin aut Iman Osman verfasserin aut Li Luo verfasserin aut Pei-Fen Kuan verfasserin aut Arshi Aurora verfasserin aut Bonnie E Gould Rothberg verfasserin aut Marcus W Bosenberg verfasserin aut Meg R Gerstenblith verfasserin aut Cheryl Thompson verfasserin aut Paul N Bogner verfasserin aut Ivan P Gorlov verfasserin aut Sheri L Holmen verfasserin aut Elise K Brunsgaard verfasserin aut Yvonne M Saenger verfasserin aut Ronglai Shen verfasserin aut Venkatraman Seshan verfasserin aut Eduardo Nagore verfasserin aut Marc S Ernstoff verfasserin aut Klaus J Busam verfasserin aut Colin B Begg verfasserin aut Nancy E Thomas verfasserin aut Marianne Berwick verfasserin aut InterMEL Consortium verfasserin aut In PLoS ONE Public Library of Science (PLoS), 2007 18(2023), 4, p e0269324 (DE-627)523574592 (DE-600)2267670-3 19326203 nnns volume:18 year:2023 number:4, p e0269324 https://doi.org/10.1371/journal.pone.0269324 kostenfrei https://doaj.org/article/2122630446b94345873b74cdda1850a8 kostenfrei https://doi.org/10.1371/journal.pone.0269324 kostenfrei https://doaj.org/toc/1932-6203 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_34 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_206 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_235 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2031 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2061 GBV_ILN_2111 GBV_ILN_2113 GBV_ILN_2190 GBV_ILN_2522 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4335 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 18 2023 4, p e0269324
allfieldsSound	10.1371/journal.pone.0269324 doi (DE-627)DOAJ089056396 (DE-599)DOAJ2122630446b94345873b74cdda1850a8 DE-627 ger DE-627 rakwb eng Irene Orlow verfasserin aut InterMEL: An international biorepository and clinical database to uncover predictors of survival in early-stage melanoma. 2023 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier <h4<Introduction</h4<We are conducting a multicenter study to identify classifiers predictive of disease-specific survival in patients with primary melanomas. Here we delineate the unique aspects, challenges, and best practices for optimizing a study of generally small-sized pigmented tumor samples including primary melanomas of at least 1.05mm from AJTCC TNM stage IIA-IIID patients. We also evaluated tissue-derived predictors of extracted nucleic acids' quality and success in downstream testing. This ongoing study will target 1,000 melanomas within the international InterMEL consortium.<h4<Methods</h4<Following a pre-established protocol, participating centers ship formalin-fixed paraffin embedded (FFPE) tissue sections to Memorial Sloan Kettering Cancer Center for the centralized handling, dermatopathology review and histology-guided coextraction of RNA and DNA. Samples are distributed for evaluation of somatic mutations using next gen sequencing (NGS) with the MSK-IMPACTTM assay, methylation-profiling (Infinium MethylationEPIC arrays), and miRNA expression (Nanostring nCounter Human v3 miRNA Expression Assay).<h4<Results</h4<Sufficient material was obtained for screening of miRNA expression in 683/685 (99%) eligible melanomas, methylation in 467 (68%), and somatic mutations in 560 (82%). In 446/685 (65%) cases, aliquots of RNA/DNA were sufficient for testing with all three platforms. Among samples evaluated by the time of this analysis, the mean NGS coverage was 249x, 59 (18.6%) samples had coverage below 100x, and 41/414 (10%) failed methylation QC due to low intensity probes or insufficient Meta-Mixed Interquartile (BMIQ)- and single sample (ss)- Noob normalizations. Six of 683 RNAs (1%) failed Nanostring QC due to the low proportion of probes above the minimum threshold. Age of the FFPE tissue blocks (p<0.001) and time elapsed from sectioning to co-extraction (p = 0.002) were associated with methylation screening failures. Melanin reduced the ability to amplify fragments of 200bp or greater (absent/lightly pigmented vs heavily pigmented, p<0.003). Conversely, heavily pigmented tumors rendered greater amounts of RNA (p<0.001), and of RNA above 200 nucleotides (p<0.001).<h4<Conclusion</h4<Our experience with many archival tissues demonstrates that with careful management of tissue processing and quality control it is possible to conduct multi-omic studies in a complex multi-institutional setting for investigations involving minute quantities of FFPE tumors, as in studies of early-stage melanoma. The study describes, for the first time, the optimal strategy for obtaining archival and limited tumor tissue, the characteristics of the nucleic acids co-extracted from a unique cell lysate, and success rate in downstream applications. In addition, our findings provide an estimate of the anticipated attrition that will guide other large multicenter research and consortia. Medicine R Science Q Keimya D Sadeghi verfasserin aut Sharon N Edmiston verfasserin aut Jessica M Kenney verfasserin aut Cecilia Lezcano verfasserin aut James S Wilmott verfasserin aut Anne E Cust verfasserin aut Richard A Scolyer verfasserin aut Graham J Mann verfasserin aut Tim K Lee verfasserin aut Hazel Burke verfasserin aut Valerie Jakrot verfasserin aut Ping Shang verfasserin aut Peter M Ferguson verfasserin aut Tawny W Boyce verfasserin aut Jennifer S Ko verfasserin aut Peter Ngo verfasserin aut Pauline Funchain verfasserin aut Judy R Rees verfasserin aut Kelli O'Connell verfasserin aut Honglin Hao verfasserin aut Eloise Parrish verfasserin aut Kathleen Conway verfasserin aut Paul B Googe verfasserin aut David W Ollila verfasserin aut Stergios J Moschos verfasserin aut Eva Hernando verfasserin aut Douglas Hanniford verfasserin aut Diana Argibay verfasserin aut Christopher I Amos verfasserin aut Jeffrey E Lee verfasserin aut Iman Osman verfasserin aut Li Luo verfasserin aut Pei-Fen Kuan verfasserin aut Arshi Aurora verfasserin aut Bonnie E Gould Rothberg verfasserin aut Marcus W Bosenberg verfasserin aut Meg R Gerstenblith verfasserin aut Cheryl Thompson verfasserin aut Paul N Bogner verfasserin aut Ivan P Gorlov verfasserin aut Sheri L Holmen verfasserin aut Elise K Brunsgaard verfasserin aut Yvonne M Saenger verfasserin aut Ronglai Shen verfasserin aut Venkatraman Seshan verfasserin aut Eduardo Nagore verfasserin aut Marc S Ernstoff verfasserin aut Klaus J Busam verfasserin aut Colin B Begg verfasserin aut Nancy E Thomas verfasserin aut Marianne Berwick verfasserin aut InterMEL Consortium verfasserin aut In PLoS ONE Public Library of Science (PLoS), 2007 18(2023), 4, p e0269324 (DE-627)523574592 (DE-600)2267670-3 19326203 nnns volume:18 year:2023 number:4, p e0269324 https://doi.org/10.1371/journal.pone.0269324 kostenfrei https://doaj.org/article/2122630446b94345873b74cdda1850a8 kostenfrei https://doi.org/10.1371/journal.pone.0269324 kostenfrei https://doaj.org/toc/1932-6203 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_34 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_206 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_235 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2031 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2061 GBV_ILN_2111 GBV_ILN_2113 GBV_ILN_2190 GBV_ILN_2522 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4335 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 18 2023 4, p e0269324
language	English
source	In PLoS ONE 18(2023), 4, p e0269324 volume:18 year:2023 number:4, p e0269324
sourceStr	In PLoS ONE 18(2023), 4, p e0269324 volume:18 year:2023 number:4, p e0269324
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container_title	PLoS ONE
authorswithroles_txt_mv	Irene Orlow @@aut@@ Keimya D Sadeghi @@aut@@ Sharon N Edmiston @@aut@@ Jessica M Kenney @@aut@@ Cecilia Lezcano @@aut@@ James S Wilmott @@aut@@ Anne E Cust @@aut@@ Richard A Scolyer @@aut@@ Graham J Mann @@aut@@ Tim K Lee @@aut@@ Hazel Burke @@aut@@ Valerie Jakrot @@aut@@ Ping Shang @@aut@@ Peter M Ferguson @@aut@@ Tawny W Boyce @@aut@@ Jennifer S Ko @@aut@@ Peter Ngo @@aut@@ Pauline Funchain @@aut@@ Judy R Rees @@aut@@ Kelli O'Connell @@aut@@ Honglin Hao @@aut@@ Eloise Parrish @@aut@@ Kathleen Conway @@aut@@ Paul B Googe @@aut@@ David W Ollila @@aut@@ Stergios J Moschos @@aut@@ Eva Hernando @@aut@@ Douglas Hanniford @@aut@@ Diana Argibay @@aut@@ Christopher I Amos @@aut@@ Jeffrey E Lee @@aut@@ Iman Osman @@aut@@ Li Luo @@aut@@ Pei-Fen Kuan @@aut@@ Arshi Aurora @@aut@@ Bonnie E Gould Rothberg @@aut@@ Marcus W Bosenberg @@aut@@ Meg R Gerstenblith @@aut@@ Cheryl Thompson @@aut@@ Paul N Bogner @@aut@@ Ivan P Gorlov @@aut@@ Sheri L Holmen @@aut@@ Elise K Brunsgaard @@aut@@ Yvonne M Saenger @@aut@@ Ronglai Shen @@aut@@ Venkatraman Seshan @@aut@@ Eduardo Nagore @@aut@@ Marc S Ernstoff @@aut@@ Klaus J Busam @@aut@@ Colin B Begg @@aut@@ Nancy E Thomas @@aut@@ Marianne Berwick @@aut@@ InterMEL Consortium @@aut@@
publishDateDaySort_date	2023-01-01T00:00:00Z
hierarchy_top_id	523574592
id	DOAJ089056396
language_de	englisch
fullrecord	<?xml version="1.0" encoding="UTF-8"?><collection xmlns="http://www.loc.gov/MARC21/slim"><record><leader>01000naa a22002652 4500</leader><controlfield tag="001">DOAJ089056396</controlfield><controlfield tag="003">DE-627</controlfield><controlfield tag="005">20230505005459.0</controlfield><controlfield tag="007">cr uuu---uuuuu</controlfield><controlfield tag="008">230505s2023 xx \|\|\|\|\|o 00\| \|\|eng c</controlfield><datafield tag="024" ind1="7" ind2=" "><subfield code="a">10.1371/journal.pone.0269324</subfield><subfield code="2">doi</subfield></datafield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(DE-627)DOAJ089056396</subfield></datafield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(DE-599)DOAJ2122630446b94345873b74cdda1850a8</subfield></datafield><datafield tag="040" ind1=" " ind2=" "><subfield code="a">DE-627</subfield><subfield code="b">ger</subfield><subfield code="c">DE-627</subfield><subfield code="e">rakwb</subfield></datafield><datafield tag="041" ind1=" " ind2=" "><subfield code="a">eng</subfield></datafield><datafield tag="100" ind1="0" ind2=" "><subfield code="a">Irene Orlow</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="245" ind1="1" ind2="0"><subfield code="a">InterMEL: An international biorepository and clinical database to uncover predictors of survival in early-stage melanoma.</subfield></datafield><datafield tag="264" ind1=" " ind2="1"><subfield code="c">2023</subfield></datafield><datafield tag="336" ind1=" " ind2=" "><subfield code="a">Text</subfield><subfield code="b">txt</subfield><subfield code="2">rdacontent</subfield></datafield><datafield tag="337" ind1=" " ind2=" "><subfield code="a">Computermedien</subfield><subfield code="b">c</subfield><subfield code="2">rdamedia</subfield></datafield><datafield tag="338" ind1=" " ind2=" "><subfield code="a">Online-Ressource</subfield><subfield code="b">cr</subfield><subfield code="2">rdacarrier</subfield></datafield><datafield tag="520" ind1=" " ind2=" "><subfield code="a"><h4<Introduction</h4<We are conducting a multicenter study to identify classifiers predictive of disease-specific survival in patients with primary melanomas. Here we delineate the unique aspects, challenges, and best practices for optimizing a study of generally small-sized pigmented tumor samples including primary melanomas of at least 1.05mm from AJTCC TNM stage IIA-IIID patients. We also evaluated tissue-derived predictors of extracted nucleic acids' quality and success in downstream testing. This ongoing study will target 1,000 melanomas within the international InterMEL consortium.<h4<Methods</h4<Following a pre-established protocol, participating centers ship formalin-fixed paraffin embedded (FFPE) tissue sections to Memorial Sloan Kettering Cancer Center for the centralized handling, dermatopathology review and histology-guided coextraction of RNA and DNA. Samples are distributed for evaluation of somatic mutations using next gen sequencing (NGS) with the MSK-IMPACTTM assay, methylation-profiling (Infinium MethylationEPIC arrays), and miRNA expression (Nanostring nCounter Human v3 miRNA Expression Assay).<h4<Results</h4<Sufficient material was obtained for screening of miRNA expression in 683/685 (99%) eligible melanomas, methylation in 467 (68%), and somatic mutations in 560 (82%). In 446/685 (65%) cases, aliquots of RNA/DNA were sufficient for testing with all three platforms. Among samples evaluated by the time of this analysis, the mean NGS coverage was 249x, 59 (18.6%) samples had coverage below 100x, and 41/414 (10%) failed methylation QC due to low intensity probes or insufficient Meta-Mixed Interquartile (BMIQ)- and single sample (ss)- Noob normalizations. Six of 683 RNAs (1%) failed Nanostring QC due to the low proportion of probes above the minimum threshold. Age of the FFPE tissue blocks (p<0.001) and time elapsed from sectioning to co-extraction (p = 0.002) were associated with methylation screening failures. Melanin reduced the ability to amplify fragments of 200bp or greater (absent/lightly pigmented vs heavily pigmented, p<0.003). Conversely, heavily pigmented tumors rendered greater amounts of RNA (p<0.001), and of RNA above 200 nucleotides (p<0.001).<h4<Conclusion</h4<Our experience with many archival tissues demonstrates that with careful management of tissue processing and quality control it is possible to conduct multi-omic studies in a complex multi-institutional setting for investigations involving minute quantities of FFPE tumors, as in studies of early-stage melanoma. The study describes, for the first time, the optimal strategy for obtaining archival and limited tumor tissue, the characteristics of the nucleic acids co-extracted from a unique cell lysate, and success rate in downstream applications. In addition, our findings provide an estimate of the anticipated attrition that will guide other large multicenter research and consortia.</subfield></datafield><datafield tag="653" ind1=" " ind2="0"><subfield code="a">Medicine</subfield></datafield><datafield tag="653" ind1=" " ind2="0"><subfield code="a">R</subfield></datafield><datafield tag="653" ind1=" " ind2="0"><subfield code="a">Science</subfield></datafield><datafield tag="653" ind1=" " ind2="0"><subfield code="a">Q</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Keimya D Sadeghi</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Sharon N Edmiston</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Jessica M Kenney</subfield><subfield code="e">verfasserin</subfield><subfield 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topic_title	InterMEL: An international biorepository and clinical database to uncover predictors of survival in early-stage melanoma
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title	InterMEL: An international biorepository and clinical database to uncover predictors of survival in early-stage melanoma.
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author_browse	Irene Orlow Keimya D Sadeghi Sharon N Edmiston Jessica M Kenney Cecilia Lezcano James S Wilmott Anne E Cust Richard A Scolyer Graham J Mann Tim K Lee Hazel Burke Valerie Jakrot Ping Shang Peter M Ferguson Tawny W Boyce Jennifer S Ko Peter Ngo Pauline Funchain Judy R Rees Kelli O'Connell Honglin Hao Eloise Parrish Kathleen Conway Paul B Googe David W Ollila Stergios J Moschos Eva Hernando Douglas Hanniford Diana Argibay Christopher I Amos Jeffrey E Lee Iman Osman Li Luo Pei-Fen Kuan Arshi Aurora Bonnie E Gould Rothberg Marcus W Bosenberg Meg R Gerstenblith Cheryl Thompson Paul N Bogner Ivan P Gorlov Sheri L Holmen Elise K Brunsgaard Yvonne M Saenger Ronglai Shen Venkatraman Seshan Eduardo Nagore Marc S Ernstoff Klaus J Busam Colin B Begg Nancy E Thomas Marianne Berwick InterMEL Consortium
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title_sort	intermel: an international biorepository and clinical database to uncover predictors of survival in early-stage melanoma
title_auth	InterMEL: An international biorepository and clinical database to uncover predictors of survival in early-stage melanoma.
abstract	<h4<Introduction</h4<We are conducting a multicenter study to identify classifiers predictive of disease-specific survival in patients with primary melanomas. Here we delineate the unique aspects, challenges, and best practices for optimizing a study of generally small-sized pigmented tumor samples including primary melanomas of at least 1.05mm from AJTCC TNM stage IIA-IIID patients. We also evaluated tissue-derived predictors of extracted nucleic acids' quality and success in downstream testing. This ongoing study will target 1,000 melanomas within the international InterMEL consortium.<h4<Methods</h4<Following a pre-established protocol, participating centers ship formalin-fixed paraffin embedded (FFPE) tissue sections to Memorial Sloan Kettering Cancer Center for the centralized handling, dermatopathology review and histology-guided coextraction of RNA and DNA. Samples are distributed for evaluation of somatic mutations using next gen sequencing (NGS) with the MSK-IMPACTTM assay, methylation-profiling (Infinium MethylationEPIC arrays), and miRNA expression (Nanostring nCounter Human v3 miRNA Expression Assay).<h4<Results</h4<Sufficient material was obtained for screening of miRNA expression in 683/685 (99%) eligible melanomas, methylation in 467 (68%), and somatic mutations in 560 (82%). In 446/685 (65%) cases, aliquots of RNA/DNA were sufficient for testing with all three platforms. Among samples evaluated by the time of this analysis, the mean NGS coverage was 249x, 59 (18.6%) samples had coverage below 100x, and 41/414 (10%) failed methylation QC due to low intensity probes or insufficient Meta-Mixed Interquartile (BMIQ)- and single sample (ss)- Noob normalizations. Six of 683 RNAs (1%) failed Nanostring QC due to the low proportion of probes above the minimum threshold. Age of the FFPE tissue blocks (p<0.001) and time elapsed from sectioning to co-extraction (p = 0.002) were associated with methylation screening failures. Melanin reduced the ability to amplify fragments of 200bp or greater (absent/lightly pigmented vs heavily pigmented, p<0.003). Conversely, heavily pigmented tumors rendered greater amounts of RNA (p<0.001), and of RNA above 200 nucleotides (p<0.001).<h4<Conclusion</h4<Our experience with many archival tissues demonstrates that with careful management of tissue processing and quality control it is possible to conduct multi-omic studies in a complex multi-institutional setting for investigations involving minute quantities of FFPE tumors, as in studies of early-stage melanoma. The study describes, for the first time, the optimal strategy for obtaining archival and limited tumor tissue, the characteristics of the nucleic acids co-extracted from a unique cell lysate, and success rate in downstream applications. In addition, our findings provide an estimate of the anticipated attrition that will guide other large multicenter research and consortia.
abstractGer	<h4<Introduction</h4<We are conducting a multicenter study to identify classifiers predictive of disease-specific survival in patients with primary melanomas. Here we delineate the unique aspects, challenges, and best practices for optimizing a study of generally small-sized pigmented tumor samples including primary melanomas of at least 1.05mm from AJTCC TNM stage IIA-IIID patients. We also evaluated tissue-derived predictors of extracted nucleic acids' quality and success in downstream testing. This ongoing study will target 1,000 melanomas within the international InterMEL consortium.<h4<Methods</h4<Following a pre-established protocol, participating centers ship formalin-fixed paraffin embedded (FFPE) tissue sections to Memorial Sloan Kettering Cancer Center for the centralized handling, dermatopathology review and histology-guided coextraction of RNA and DNA. Samples are distributed for evaluation of somatic mutations using next gen sequencing (NGS) with the MSK-IMPACTTM assay, methylation-profiling (Infinium MethylationEPIC arrays), and miRNA expression (Nanostring nCounter Human v3 miRNA Expression Assay).<h4<Results</h4<Sufficient material was obtained for screening of miRNA expression in 683/685 (99%) eligible melanomas, methylation in 467 (68%), and somatic mutations in 560 (82%). In 446/685 (65%) cases, aliquots of RNA/DNA were sufficient for testing with all three platforms. Among samples evaluated by the time of this analysis, the mean NGS coverage was 249x, 59 (18.6%) samples had coverage below 100x, and 41/414 (10%) failed methylation QC due to low intensity probes or insufficient Meta-Mixed Interquartile (BMIQ)- and single sample (ss)- Noob normalizations. Six of 683 RNAs (1%) failed Nanostring QC due to the low proportion of probes above the minimum threshold. Age of the FFPE tissue blocks (p<0.001) and time elapsed from sectioning to co-extraction (p = 0.002) were associated with methylation screening failures. Melanin reduced the ability to amplify fragments of 200bp or greater (absent/lightly pigmented vs heavily pigmented, p<0.003). Conversely, heavily pigmented tumors rendered greater amounts of RNA (p<0.001), and of RNA above 200 nucleotides (p<0.001).<h4<Conclusion</h4<Our experience with many archival tissues demonstrates that with careful management of tissue processing and quality control it is possible to conduct multi-omic studies in a complex multi-institutional setting for investigations involving minute quantities of FFPE tumors, as in studies of early-stage melanoma. The study describes, for the first time, the optimal strategy for obtaining archival and limited tumor tissue, the characteristics of the nucleic acids co-extracted from a unique cell lysate, and success rate in downstream applications. In addition, our findings provide an estimate of the anticipated attrition that will guide other large multicenter research and consortia.
abstract_unstemmed	<h4<Introduction</h4<We are conducting a multicenter study to identify classifiers predictive of disease-specific survival in patients with primary melanomas. Here we delineate the unique aspects, challenges, and best practices for optimizing a study of generally small-sized pigmented tumor samples including primary melanomas of at least 1.05mm from AJTCC TNM stage IIA-IIID patients. We also evaluated tissue-derived predictors of extracted nucleic acids' quality and success in downstream testing. This ongoing study will target 1,000 melanomas within the international InterMEL consortium.<h4<Methods</h4<Following a pre-established protocol, participating centers ship formalin-fixed paraffin embedded (FFPE) tissue sections to Memorial Sloan Kettering Cancer Center for the centralized handling, dermatopathology review and histology-guided coextraction of RNA and DNA. Samples are distributed for evaluation of somatic mutations using next gen sequencing (NGS) with the MSK-IMPACTTM assay, methylation-profiling (Infinium MethylationEPIC arrays), and miRNA expression (Nanostring nCounter Human v3 miRNA Expression Assay).<h4<Results</h4<Sufficient material was obtained for screening of miRNA expression in 683/685 (99%) eligible melanomas, methylation in 467 (68%), and somatic mutations in 560 (82%). In 446/685 (65%) cases, aliquots of RNA/DNA were sufficient for testing with all three platforms. Among samples evaluated by the time of this analysis, the mean NGS coverage was 249x, 59 (18.6%) samples had coverage below 100x, and 41/414 (10%) failed methylation QC due to low intensity probes or insufficient Meta-Mixed Interquartile (BMIQ)- and single sample (ss)- Noob normalizations. Six of 683 RNAs (1%) failed Nanostring QC due to the low proportion of probes above the minimum threshold. Age of the FFPE tissue blocks (p<0.001) and time elapsed from sectioning to co-extraction (p = 0.002) were associated with methylation screening failures. Melanin reduced the ability to amplify fragments of 200bp or greater (absent/lightly pigmented vs heavily pigmented, p<0.003). Conversely, heavily pigmented tumors rendered greater amounts of RNA (p<0.001), and of RNA above 200 nucleotides (p<0.001).<h4<Conclusion</h4<Our experience with many archival tissues demonstrates that with careful management of tissue processing and quality control it is possible to conduct multi-omic studies in a complex multi-institutional setting for investigations involving minute quantities of FFPE tumors, as in studies of early-stage melanoma. The study describes, for the first time, the optimal strategy for obtaining archival and limited tumor tissue, the characteristics of the nucleic acids co-extracted from a unique cell lysate, and success rate in downstream applications. In addition, our findings provide an estimate of the anticipated attrition that will guide other large multicenter research and consortia.
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title_short	InterMEL: An international biorepository and clinical database to uncover predictors of survival in early-stage melanoma.
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