Comprehensive routine diagnostic screening to identify predictive mutations, gene amplifications, and microsatellite instability in FFPE tumor material

Background Sensitive and reliable molecular diagnostics is needed to guide therapeutic decisions for cancer patients. Although less material becomes available for testing, genetic markers are rapidly expanding. Simultaneous detection of predictive markers, including mutations, gene amplifications and MSI, will save valuable material, time and costs. Methods Using a single-molecule molecular inversion probe (smMIP)-based targeted next-generation sequencing (NGS) approach, we developed an NGS panel allowing detection of predictive mutations in 33 genes, gene amplifications of 13 genes and microsatellite instability (MSI) by the evaluation of 55 microsatellite markers. The panel was designed to target all clinically relevant single and multiple nucleotide mutations in routinely available lung cancer, colorectal cancer, melanoma, and gastro-intestinal stromal tumor samples, but is useful for a broader set of tumor types. Results The smMIP-based NGS panel was successfully validated and cut-off values were established for reliable gene amplification analysis (i.e. relative coverage ≥3) and MSI detection (≥30% unstable loci). After validation, 728 routine diagnostic tumor samples including a broad range of tumor types were sequenced with sufficient sensitivity (2.4% drop-out), including samples with low DNA input (< 10 ng; 88% successful), low tumor purity (5–10%; 77% successful), and cytological material (90% successful). 75% of these tumor samples showed ≥1 (likely) pathogenic mutation, including targetable mutations (e.g. EGFR, BRAF, MET, ERBB2, KIT, PDGFRA). Amplifications were observed in 5.5% of the samples, comprising clinically relevant amplifications (e.g. MET, ERBB2, FGFR1). 1.5% of the tumor samples were classified as MSI-high, including both MSI-prone and non-MSI-prone tumors. Conclusions We developed a comprehensive workflow for predictive analysis of diagnostic tumor samples. The smMIP-based NGS analysis was shown suitable for limited amounts of histological and cytological material. As smMIP technology allows easy adaptation of panels, this approach can comply with the rapidly expanding molecular markers. Ausführliche Beschreibung

Gespeichert in:

Autor*in:	Steeghs, Elisabeth M. P. [verfasserIn] Kroeze, Leonie I. [verfasserIn] Tops, Bastiaan B. J. [verfasserIn] van Kempen, Leon C. [verfasserIn] ter Elst, Arja [verfasserIn] Kastner-van Raaij, Annemiek W. M. [verfasserIn] Hendriks-Cornelissen, Sandra J. B. [verfasserIn] Hermsen, Mandy J. W. [verfasserIn] Jansen, Erik A. M. [verfasserIn] Nederlof, Petra M. [verfasserIn] Schuuring, Ed [verfasserIn] Ligtenberg, Marjolijn J. L. [verfasserIn] Eijkelenboom, Astrid [verfasserIn]

Format:	E-Artikel
Sprache:	Englisch

Erschienen:	2020

Schlagwörter:	Predictive analysis Next-generation sequencing Mutation Gene amplification Microsatellite instability FFPE Melanoma GIST Colorectal carcinoma Lung cancer

Übergeordnetes Werk:	Enthalten in: BMC cancer - London : BioMed Central, 2001, 20(2020), 1 vom: 07. Apr.
Übergeordnetes Werk:	volume:20 ; year:2020 ; number:1 ; day:07 ; month:04

Links:	Volltext

DOI / URN:	10.1186/s12885-020-06785-6

Katalog-ID:	SPR039348423

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245	1	0	\|a Comprehensive routine diagnostic screening to identify predictive mutations, gene amplifications, and microsatellite instability in FFPE tumor material
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520			\|a Background Sensitive and reliable molecular diagnostics is needed to guide therapeutic decisions for cancer patients. Although less material becomes available for testing, genetic markers are rapidly expanding. Simultaneous detection of predictive markers, including mutations, gene amplifications and MSI, will save valuable material, time and costs. Methods Using a single-molecule molecular inversion probe (smMIP)-based targeted next-generation sequencing (NGS) approach, we developed an NGS panel allowing detection of predictive mutations in 33 genes, gene amplifications of 13 genes and microsatellite instability (MSI) by the evaluation of 55 microsatellite markers. The panel was designed to target all clinically relevant single and multiple nucleotide mutations in routinely available lung cancer, colorectal cancer, melanoma, and gastro-intestinal stromal tumor samples, but is useful for a broader set of tumor types. Results The smMIP-based NGS panel was successfully validated and cut-off values were established for reliable gene amplification analysis (i.e. relative coverage ≥3) and MSI detection (≥30% unstable loci). After validation, 728 routine diagnostic tumor samples including a broad range of tumor types were sequenced with sufficient sensitivity (2.4% drop-out), including samples with low DNA input (< 10 ng; 88% successful), low tumor purity (5–10%; 77% successful), and cytological material (90% successful). 75% of these tumor samples showed ≥1 (likely) pathogenic mutation, including targetable mutations (e.g. EGFR, BRAF, MET, ERBB2, KIT, PDGFRA). Amplifications were observed in 5.5% of the samples, comprising clinically relevant amplifications (e.g. MET, ERBB2, FGFR1). 1.5% of the tumor samples were classified as MSI-high, including both MSI-prone and non-MSI-prone tumors. Conclusions We developed a comprehensive workflow for predictive analysis of diagnostic tumor samples. The smMIP-based NGS analysis was shown suitable for limited amounts of histological and cytological material. As smMIP technology allows easy adaptation of panels, this approach can comply with the rapidly expanding molecular markers.
650		4	\|a Predictive analysis \|7 (dpeaa)DE-He213
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650		4	\|a GIST \|7 (dpeaa)DE-He213
650		4	\|a Colorectal carcinoma \|7 (dpeaa)DE-He213
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700	1		\|a Kroeze, Leonie I. \|e verfasserin \|4 aut
700	1		\|a Tops, Bastiaan B. J. \|e verfasserin \|4 aut
700	1		\|a van Kempen, Leon C. \|e verfasserin \|4 aut
700	1		\|a ter Elst, Arja \|e verfasserin \|4 aut
700	1		\|a Kastner-van Raaij, Annemiek W. M. \|e verfasserin \|4 aut
700	1		\|a Hendriks-Cornelissen, Sandra J. B. \|e verfasserin \|4 aut
700	1		\|a Hermsen, Mandy J. W. \|e verfasserin \|4 aut
700	1		\|a Jansen, Erik A. M. \|e verfasserin \|4 aut
700	1		\|a Nederlof, Petra M. \|e verfasserin \|4 aut
700	1		\|a Schuuring, Ed \|e verfasserin \|4 aut
700	1		\|a Ligtenberg, Marjolijn J. L. \|e verfasserin \|4 aut
700	1		\|a Eijkelenboom, Astrid \|e verfasserin \|4 aut
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allfields	10.1186/s12885-020-06785-6 doi (DE-627)SPR039348423 (SPR)s12885-020-06785-6-e DE-627 ger DE-627 rakwb eng 610 ASE 44.00 bkl Steeghs, Elisabeth M. P. verfasserin aut Comprehensive routine diagnostic screening to identify predictive mutations, gene amplifications, and microsatellite instability in FFPE tumor material 2020 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Background Sensitive and reliable molecular diagnostics is needed to guide therapeutic decisions for cancer patients. Although less material becomes available for testing, genetic markers are rapidly expanding. Simultaneous detection of predictive markers, including mutations, gene amplifications and MSI, will save valuable material, time and costs. Methods Using a single-molecule molecular inversion probe (smMIP)-based targeted next-generation sequencing (NGS) approach, we developed an NGS panel allowing detection of predictive mutations in 33 genes, gene amplifications of 13 genes and microsatellite instability (MSI) by the evaluation of 55 microsatellite markers. The panel was designed to target all clinically relevant single and multiple nucleotide mutations in routinely available lung cancer, colorectal cancer, melanoma, and gastro-intestinal stromal tumor samples, but is useful for a broader set of tumor types. Results The smMIP-based NGS panel was successfully validated and cut-off values were established for reliable gene amplification analysis (i.e. relative coverage ≥3) and MSI detection (≥30% unstable loci). After validation, 728 routine diagnostic tumor samples including a broad range of tumor types were sequenced with sufficient sensitivity (2.4% drop-out), including samples with low DNA input (< 10 ng; 88% successful), low tumor purity (5–10%; 77% successful), and cytological material (90% successful). 75% of these tumor samples showed ≥1 (likely) pathogenic mutation, including targetable mutations (e.g. EGFR, BRAF, MET, ERBB2, KIT, PDGFRA). Amplifications were observed in 5.5% of the samples, comprising clinically relevant amplifications (e.g. MET, ERBB2, FGFR1). 1.5% of the tumor samples were classified as MSI-high, including both MSI-prone and non-MSI-prone tumors. Conclusions We developed a comprehensive workflow for predictive analysis of diagnostic tumor samples. The smMIP-based NGS analysis was shown suitable for limited amounts of histological and cytological material. As smMIP technology allows easy adaptation of panels, this approach can comply with the rapidly expanding molecular markers. Predictive analysis (dpeaa)DE-He213 Next-generation sequencing (dpeaa)DE-He213 Mutation (dpeaa)DE-He213 Gene amplification (dpeaa)DE-He213 Microsatellite instability (dpeaa)DE-He213 FFPE (dpeaa)DE-He213 Melanoma (dpeaa)DE-He213 GIST (dpeaa)DE-He213 Colorectal carcinoma (dpeaa)DE-He213 Lung cancer (dpeaa)DE-He213 Kroeze, Leonie I. verfasserin aut Tops, Bastiaan B. J. verfasserin aut van Kempen, Leon C. verfasserin aut ter Elst, Arja verfasserin aut Kastner-van Raaij, Annemiek W. M. verfasserin aut Hendriks-Cornelissen, Sandra J. B. verfasserin aut Hermsen, Mandy J. W. verfasserin aut Jansen, Erik A. M. verfasserin aut Nederlof, Petra M. verfasserin aut Schuuring, Ed verfasserin aut Ligtenberg, Marjolijn J. L. verfasserin aut Eijkelenboom, Astrid verfasserin aut Enthalten in BMC cancer London : BioMed Central, 2001 20(2020), 1 vom: 07. Apr. (DE-627)326643710 (DE-600)2041352-X 1471-2407 nnns volume:20 year:2020 number:1 day:07 month:04 https://dx.doi.org/10.1186/s12885-020-06785-6 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 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_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 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_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_4338 GBV_ILN_4367 GBV_ILN_4700 44.00 ASE AR 20 2020 1 07 04
spelling	10.1186/s12885-020-06785-6 doi (DE-627)SPR039348423 (SPR)s12885-020-06785-6-e DE-627 ger DE-627 rakwb eng 610 ASE 44.00 bkl Steeghs, Elisabeth M. P. verfasserin aut Comprehensive routine diagnostic screening to identify predictive mutations, gene amplifications, and microsatellite instability in FFPE tumor material 2020 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Background Sensitive and reliable molecular diagnostics is needed to guide therapeutic decisions for cancer patients. Although less material becomes available for testing, genetic markers are rapidly expanding. Simultaneous detection of predictive markers, including mutations, gene amplifications and MSI, will save valuable material, time and costs. Methods Using a single-molecule molecular inversion probe (smMIP)-based targeted next-generation sequencing (NGS) approach, we developed an NGS panel allowing detection of predictive mutations in 33 genes, gene amplifications of 13 genes and microsatellite instability (MSI) by the evaluation of 55 microsatellite markers. The panel was designed to target all clinically relevant single and multiple nucleotide mutations in routinely available lung cancer, colorectal cancer, melanoma, and gastro-intestinal stromal tumor samples, but is useful for a broader set of tumor types. Results The smMIP-based NGS panel was successfully validated and cut-off values were established for reliable gene amplification analysis (i.e. relative coverage ≥3) and MSI detection (≥30% unstable loci). After validation, 728 routine diagnostic tumor samples including a broad range of tumor types were sequenced with sufficient sensitivity (2.4% drop-out), including samples with low DNA input (< 10 ng; 88% successful), low tumor purity (5–10%; 77% successful), and cytological material (90% successful). 75% of these tumor samples showed ≥1 (likely) pathogenic mutation, including targetable mutations (e.g. EGFR, BRAF, MET, ERBB2, KIT, PDGFRA). Amplifications were observed in 5.5% of the samples, comprising clinically relevant amplifications (e.g. MET, ERBB2, FGFR1). 1.5% of the tumor samples were classified as MSI-high, including both MSI-prone and non-MSI-prone tumors. Conclusions We developed a comprehensive workflow for predictive analysis of diagnostic tumor samples. The smMIP-based NGS analysis was shown suitable for limited amounts of histological and cytological material. As smMIP technology allows easy adaptation of panels, this approach can comply with the rapidly expanding molecular markers. Predictive analysis (dpeaa)DE-He213 Next-generation sequencing (dpeaa)DE-He213 Mutation (dpeaa)DE-He213 Gene amplification (dpeaa)DE-He213 Microsatellite instability (dpeaa)DE-He213 FFPE (dpeaa)DE-He213 Melanoma (dpeaa)DE-He213 GIST (dpeaa)DE-He213 Colorectal carcinoma (dpeaa)DE-He213 Lung cancer (dpeaa)DE-He213 Kroeze, Leonie I. verfasserin aut Tops, Bastiaan B. J. verfasserin aut van Kempen, Leon C. verfasserin aut ter Elst, Arja verfasserin aut Kastner-van Raaij, Annemiek W. M. verfasserin aut Hendriks-Cornelissen, Sandra J. B. verfasserin aut Hermsen, Mandy J. W. verfasserin aut Jansen, Erik A. M. verfasserin aut Nederlof, Petra M. verfasserin aut Schuuring, Ed verfasserin aut Ligtenberg, Marjolijn J. L. verfasserin aut Eijkelenboom, Astrid verfasserin aut Enthalten in BMC cancer London : BioMed Central, 2001 20(2020), 1 vom: 07. Apr. (DE-627)326643710 (DE-600)2041352-X 1471-2407 nnns volume:20 year:2020 number:1 day:07 month:04 https://dx.doi.org/10.1186/s12885-020-06785-6 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 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_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 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_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_4338 GBV_ILN_4367 GBV_ILN_4700 44.00 ASE AR 20 2020 1 07 04
allfields_unstemmed	10.1186/s12885-020-06785-6 doi (DE-627)SPR039348423 (SPR)s12885-020-06785-6-e DE-627 ger DE-627 rakwb eng 610 ASE 44.00 bkl Steeghs, Elisabeth M. P. verfasserin aut Comprehensive routine diagnostic screening to identify predictive mutations, gene amplifications, and microsatellite instability in FFPE tumor material 2020 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Background Sensitive and reliable molecular diagnostics is needed to guide therapeutic decisions for cancer patients. Although less material becomes available for testing, genetic markers are rapidly expanding. Simultaneous detection of predictive markers, including mutations, gene amplifications and MSI, will save valuable material, time and costs. Methods Using a single-molecule molecular inversion probe (smMIP)-based targeted next-generation sequencing (NGS) approach, we developed an NGS panel allowing detection of predictive mutations in 33 genes, gene amplifications of 13 genes and microsatellite instability (MSI) by the evaluation of 55 microsatellite markers. The panel was designed to target all clinically relevant single and multiple nucleotide mutations in routinely available lung cancer, colorectal cancer, melanoma, and gastro-intestinal stromal tumor samples, but is useful for a broader set of tumor types. Results The smMIP-based NGS panel was successfully validated and cut-off values were established for reliable gene amplification analysis (i.e. relative coverage ≥3) and MSI detection (≥30% unstable loci). After validation, 728 routine diagnostic tumor samples including a broad range of tumor types were sequenced with sufficient sensitivity (2.4% drop-out), including samples with low DNA input (< 10 ng; 88% successful), low tumor purity (5–10%; 77% successful), and cytological material (90% successful). 75% of these tumor samples showed ≥1 (likely) pathogenic mutation, including targetable mutations (e.g. EGFR, BRAF, MET, ERBB2, KIT, PDGFRA). Amplifications were observed in 5.5% of the samples, comprising clinically relevant amplifications (e.g. MET, ERBB2, FGFR1). 1.5% of the tumor samples were classified as MSI-high, including both MSI-prone and non-MSI-prone tumors. Conclusions We developed a comprehensive workflow for predictive analysis of diagnostic tumor samples. The smMIP-based NGS analysis was shown suitable for limited amounts of histological and cytological material. As smMIP technology allows easy adaptation of panels, this approach can comply with the rapidly expanding molecular markers. Predictive analysis (dpeaa)DE-He213 Next-generation sequencing (dpeaa)DE-He213 Mutation (dpeaa)DE-He213 Gene amplification (dpeaa)DE-He213 Microsatellite instability (dpeaa)DE-He213 FFPE (dpeaa)DE-He213 Melanoma (dpeaa)DE-He213 GIST (dpeaa)DE-He213 Colorectal carcinoma (dpeaa)DE-He213 Lung cancer (dpeaa)DE-He213 Kroeze, Leonie I. verfasserin aut Tops, Bastiaan B. J. verfasserin aut van Kempen, Leon C. verfasserin aut ter Elst, Arja verfasserin aut Kastner-van Raaij, Annemiek W. M. verfasserin aut Hendriks-Cornelissen, Sandra J. B. verfasserin aut Hermsen, Mandy J. W. verfasserin aut Jansen, Erik A. M. verfasserin aut Nederlof, Petra M. verfasserin aut Schuuring, Ed verfasserin aut Ligtenberg, Marjolijn J. L. verfasserin aut Eijkelenboom, Astrid verfasserin aut Enthalten in BMC cancer London : BioMed Central, 2001 20(2020), 1 vom: 07. Apr. (DE-627)326643710 (DE-600)2041352-X 1471-2407 nnns volume:20 year:2020 number:1 day:07 month:04 https://dx.doi.org/10.1186/s12885-020-06785-6 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 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_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 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_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_4338 GBV_ILN_4367 GBV_ILN_4700 44.00 ASE AR 20 2020 1 07 04
allfieldsGer	10.1186/s12885-020-06785-6 doi (DE-627)SPR039348423 (SPR)s12885-020-06785-6-e DE-627 ger DE-627 rakwb eng 610 ASE 44.00 bkl Steeghs, Elisabeth M. P. verfasserin aut Comprehensive routine diagnostic screening to identify predictive mutations, gene amplifications, and microsatellite instability in FFPE tumor material 2020 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Background Sensitive and reliable molecular diagnostics is needed to guide therapeutic decisions for cancer patients. Although less material becomes available for testing, genetic markers are rapidly expanding. Simultaneous detection of predictive markers, including mutations, gene amplifications and MSI, will save valuable material, time and costs. Methods Using a single-molecule molecular inversion probe (smMIP)-based targeted next-generation sequencing (NGS) approach, we developed an NGS panel allowing detection of predictive mutations in 33 genes, gene amplifications of 13 genes and microsatellite instability (MSI) by the evaluation of 55 microsatellite markers. The panel was designed to target all clinically relevant single and multiple nucleotide mutations in routinely available lung cancer, colorectal cancer, melanoma, and gastro-intestinal stromal tumor samples, but is useful for a broader set of tumor types. Results The smMIP-based NGS panel was successfully validated and cut-off values were established for reliable gene amplification analysis (i.e. relative coverage ≥3) and MSI detection (≥30% unstable loci). After validation, 728 routine diagnostic tumor samples including a broad range of tumor types were sequenced with sufficient sensitivity (2.4% drop-out), including samples with low DNA input (< 10 ng; 88% successful), low tumor purity (5–10%; 77% successful), and cytological material (90% successful). 75% of these tumor samples showed ≥1 (likely) pathogenic mutation, including targetable mutations (e.g. EGFR, BRAF, MET, ERBB2, KIT, PDGFRA). Amplifications were observed in 5.5% of the samples, comprising clinically relevant amplifications (e.g. MET, ERBB2, FGFR1). 1.5% of the tumor samples were classified as MSI-high, including both MSI-prone and non-MSI-prone tumors. Conclusions We developed a comprehensive workflow for predictive analysis of diagnostic tumor samples. The smMIP-based NGS analysis was shown suitable for limited amounts of histological and cytological material. As smMIP technology allows easy adaptation of panels, this approach can comply with the rapidly expanding molecular markers. Predictive analysis (dpeaa)DE-He213 Next-generation sequencing (dpeaa)DE-He213 Mutation (dpeaa)DE-He213 Gene amplification (dpeaa)DE-He213 Microsatellite instability (dpeaa)DE-He213 FFPE (dpeaa)DE-He213 Melanoma (dpeaa)DE-He213 GIST (dpeaa)DE-He213 Colorectal carcinoma (dpeaa)DE-He213 Lung cancer (dpeaa)DE-He213 Kroeze, Leonie I. verfasserin aut Tops, Bastiaan B. J. verfasserin aut van Kempen, Leon C. verfasserin aut ter Elst, Arja verfasserin aut Kastner-van Raaij, Annemiek W. M. verfasserin aut Hendriks-Cornelissen, Sandra J. B. verfasserin aut Hermsen, Mandy J. W. verfasserin aut Jansen, Erik A. M. verfasserin aut Nederlof, Petra M. verfasserin aut Schuuring, Ed verfasserin aut Ligtenberg, Marjolijn J. L. verfasserin aut Eijkelenboom, Astrid verfasserin aut Enthalten in BMC cancer London : BioMed Central, 2001 20(2020), 1 vom: 07. Apr. (DE-627)326643710 (DE-600)2041352-X 1471-2407 nnns volume:20 year:2020 number:1 day:07 month:04 https://dx.doi.org/10.1186/s12885-020-06785-6 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 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_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 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_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_4338 GBV_ILN_4367 GBV_ILN_4700 44.00 ASE AR 20 2020 1 07 04
allfieldsSound	10.1186/s12885-020-06785-6 doi (DE-627)SPR039348423 (SPR)s12885-020-06785-6-e DE-627 ger DE-627 rakwb eng 610 ASE 44.00 bkl Steeghs, Elisabeth M. P. verfasserin aut Comprehensive routine diagnostic screening to identify predictive mutations, gene amplifications, and microsatellite instability in FFPE tumor material 2020 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Background Sensitive and reliable molecular diagnostics is needed to guide therapeutic decisions for cancer patients. Although less material becomes available for testing, genetic markers are rapidly expanding. Simultaneous detection of predictive markers, including mutations, gene amplifications and MSI, will save valuable material, time and costs. Methods Using a single-molecule molecular inversion probe (smMIP)-based targeted next-generation sequencing (NGS) approach, we developed an NGS panel allowing detection of predictive mutations in 33 genes, gene amplifications of 13 genes and microsatellite instability (MSI) by the evaluation of 55 microsatellite markers. The panel was designed to target all clinically relevant single and multiple nucleotide mutations in routinely available lung cancer, colorectal cancer, melanoma, and gastro-intestinal stromal tumor samples, but is useful for a broader set of tumor types. Results The smMIP-based NGS panel was successfully validated and cut-off values were established for reliable gene amplification analysis (i.e. relative coverage ≥3) and MSI detection (≥30% unstable loci). After validation, 728 routine diagnostic tumor samples including a broad range of tumor types were sequenced with sufficient sensitivity (2.4% drop-out), including samples with low DNA input (< 10 ng; 88% successful), low tumor purity (5–10%; 77% successful), and cytological material (90% successful). 75% of these tumor samples showed ≥1 (likely) pathogenic mutation, including targetable mutations (e.g. EGFR, BRAF, MET, ERBB2, KIT, PDGFRA). Amplifications were observed in 5.5% of the samples, comprising clinically relevant amplifications (e.g. MET, ERBB2, FGFR1). 1.5% of the tumor samples were classified as MSI-high, including both MSI-prone and non-MSI-prone tumors. Conclusions We developed a comprehensive workflow for predictive analysis of diagnostic tumor samples. The smMIP-based NGS analysis was shown suitable for limited amounts of histological and cytological material. As smMIP technology allows easy adaptation of panels, this approach can comply with the rapidly expanding molecular markers. Predictive analysis (dpeaa)DE-He213 Next-generation sequencing (dpeaa)DE-He213 Mutation (dpeaa)DE-He213 Gene amplification (dpeaa)DE-He213 Microsatellite instability (dpeaa)DE-He213 FFPE (dpeaa)DE-He213 Melanoma (dpeaa)DE-He213 GIST (dpeaa)DE-He213 Colorectal carcinoma (dpeaa)DE-He213 Lung cancer (dpeaa)DE-He213 Kroeze, Leonie I. verfasserin aut Tops, Bastiaan B. J. verfasserin aut van Kempen, Leon C. verfasserin aut ter Elst, Arja verfasserin aut Kastner-van Raaij, Annemiek W. M. verfasserin aut Hendriks-Cornelissen, Sandra J. B. verfasserin aut Hermsen, Mandy J. W. verfasserin aut Jansen, Erik A. M. verfasserin aut Nederlof, Petra M. verfasserin aut Schuuring, Ed verfasserin aut Ligtenberg, Marjolijn J. L. verfasserin aut Eijkelenboom, Astrid verfasserin aut Enthalten in BMC cancer London : BioMed Central, 2001 20(2020), 1 vom: 07. Apr. (DE-627)326643710 (DE-600)2041352-X 1471-2407 nnns volume:20 year:2020 number:1 day:07 month:04 https://dx.doi.org/10.1186/s12885-020-06785-6 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 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_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 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_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_4338 GBV_ILN_4367 GBV_ILN_4700 44.00 ASE AR 20 2020 1 07 04
language	English
source	Enthalten in BMC cancer 20(2020), 1 vom: 07. Apr. volume:20 year:2020 number:1 day:07 month:04
sourceStr	Enthalten in BMC cancer 20(2020), 1 vom: 07. Apr. volume:20 year:2020 number:1 day:07 month:04
format_phy_str_mv	Article
institution	findex.gbv.de
topic_facet	Predictive analysis Next-generation sequencing Mutation Gene amplification Microsatellite instability FFPE Melanoma GIST Colorectal carcinoma Lung cancer
dewey-raw	610
isfreeaccess_bool	true
container_title	BMC cancer
authorswithroles_txt_mv	Steeghs, Elisabeth M. P. @@aut@@ Kroeze, Leonie I. @@aut@@ Tops, Bastiaan B. J. @@aut@@ van Kempen, Leon C. @@aut@@ ter Elst, Arja @@aut@@ Kastner-van Raaij, Annemiek W. M. @@aut@@ Hendriks-Cornelissen, Sandra J. B. @@aut@@ Hermsen, Mandy J. W. @@aut@@ Jansen, Erik A. M. @@aut@@ Nederlof, Petra M. @@aut@@ Schuuring, Ed @@aut@@ Ligtenberg, Marjolijn J. L. @@aut@@ Eijkelenboom, Astrid @@aut@@
publishDateDaySort_date	2020-04-07T00:00:00Z
hierarchy_top_id	326643710
dewey-sort	3610
id	SPR039348423
language_de	englisch
fullrecord	<?xml version="1.0" encoding="UTF-8"?><collection xmlns="http://www.loc.gov/MARC21/slim"><record><leader>01000caa a22002652 4500</leader><controlfield tag="001">SPR039348423</controlfield><controlfield tag="003">DE-627</controlfield><controlfield tag="005">20230519161838.0</controlfield><controlfield tag="007">cr uuu---uuuuu</controlfield><controlfield tag="008">201007s2020 xx \|\|\|\|\|o 00\| \|\|eng c</controlfield><datafield tag="024" ind1="7" ind2=" "><subfield code="a">10.1186/s12885-020-06785-6</subfield><subfield code="2">doi</subfield></datafield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(DE-627)SPR039348423</subfield></datafield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(SPR)s12885-020-06785-6-e</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="082" ind1="0" ind2="4"><subfield code="a">610</subfield><subfield code="q">ASE</subfield></datafield><datafield tag="084" ind1=" " ind2=" "><subfield code="a">44.00</subfield><subfield code="2">bkl</subfield></datafield><datafield tag="100" ind1="1" ind2=" "><subfield code="a">Steeghs, Elisabeth M. P.</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="245" ind1="1" ind2="0"><subfield code="a">Comprehensive routine diagnostic screening to identify predictive mutations, gene amplifications, and microsatellite instability in FFPE tumor material</subfield></datafield><datafield tag="264" ind1=" " ind2="1"><subfield code="c">2020</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">Background Sensitive and reliable molecular diagnostics is needed to guide therapeutic decisions for cancer patients. Although less material becomes available for testing, genetic markers are rapidly expanding. Simultaneous detection of predictive markers, including mutations, gene amplifications and MSI, will save valuable material, time and costs. Methods Using a single-molecule molecular inversion probe (smMIP)-based targeted next-generation sequencing (NGS) approach, we developed an NGS panel allowing detection of predictive mutations in 33 genes, gene amplifications of 13 genes and microsatellite instability (MSI) by the evaluation of 55 microsatellite markers. The panel was designed to target all clinically relevant single and multiple nucleotide mutations in routinely available lung cancer, colorectal cancer, melanoma, and gastro-intestinal stromal tumor samples, but is useful for a broader set of tumor types. Results The smMIP-based NGS panel was successfully validated and cut-off values were established for reliable gene amplification analysis (i.e. relative coverage ≥3) and MSI detection (≥30% unstable loci). After validation, 728 routine diagnostic tumor samples including a broad range of tumor types were sequenced with sufficient sensitivity (2.4% drop-out), including samples with low DNA input (< 10 ng; 88% successful), low tumor purity (5–10%; 77% successful), and cytological material (90% successful). 75% of these tumor samples showed ≥1 (likely) pathogenic mutation, including targetable mutations (e.g. EGFR, BRAF, MET, ERBB2, KIT, PDGFRA). Amplifications were observed in 5.5% of the samples, comprising clinically relevant amplifications (e.g. MET, ERBB2, FGFR1). 1.5% of the tumor samples were classified as MSI-high, including both MSI-prone and non-MSI-prone tumors. Conclusions We developed a comprehensive workflow for predictive analysis of diagnostic tumor samples. The smMIP-based NGS analysis was shown suitable for limited amounts of histological and cytological material. 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author	Steeghs, Elisabeth M. P.
spellingShingle	Steeghs, Elisabeth M. P. ddc 610 bkl 44.00 misc Predictive analysis misc Next-generation sequencing misc Mutation misc Gene amplification misc Microsatellite instability misc FFPE misc Melanoma misc GIST misc Colorectal carcinoma misc Lung cancer Comprehensive routine diagnostic screening to identify predictive mutations, gene amplifications, and microsatellite instability in FFPE tumor material
authorStr	Steeghs, Elisabeth M. P.
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topic_title	610 ASE 44.00 bkl Comprehensive routine diagnostic screening to identify predictive mutations, gene amplifications, and microsatellite instability in FFPE tumor material Predictive analysis (dpeaa)DE-He213 Next-generation sequencing (dpeaa)DE-He213 Mutation (dpeaa)DE-He213 Gene amplification (dpeaa)DE-He213 Microsatellite instability (dpeaa)DE-He213 FFPE (dpeaa)DE-He213 Melanoma (dpeaa)DE-He213 GIST (dpeaa)DE-He213 Colorectal carcinoma (dpeaa)DE-He213 Lung cancer (dpeaa)DE-He213
topic	ddc 610 bkl 44.00 misc Predictive analysis misc Next-generation sequencing misc Mutation misc Gene amplification misc Microsatellite instability misc FFPE misc Melanoma misc GIST misc Colorectal carcinoma misc Lung cancer
topic_unstemmed	ddc 610 bkl 44.00 misc Predictive analysis misc Next-generation sequencing misc Mutation misc Gene amplification misc Microsatellite instability misc FFPE misc Melanoma misc GIST misc Colorectal carcinoma misc Lung cancer
topic_browse	ddc 610 bkl 44.00 misc Predictive analysis misc Next-generation sequencing misc Mutation misc Gene amplification misc Microsatellite instability misc FFPE misc Melanoma misc GIST misc Colorectal carcinoma misc Lung cancer
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title	Comprehensive routine diagnostic screening to identify predictive mutations, gene amplifications, and microsatellite instability in FFPE tumor material
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title_full	Comprehensive routine diagnostic screening to identify predictive mutations, gene amplifications, and microsatellite instability in FFPE tumor material
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author_browse	Steeghs, Elisabeth M. P. Kroeze, Leonie I. Tops, Bastiaan B. J. van Kempen, Leon C. ter Elst, Arja Kastner-van Raaij, Annemiek W. M. Hendriks-Cornelissen, Sandra J. B. Hermsen, Mandy J. W. Jansen, Erik A. M. Nederlof, Petra M. Schuuring, Ed Ligtenberg, Marjolijn J. L. Eijkelenboom, Astrid
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title_sort	comprehensive routine diagnostic screening to identify predictive mutations, gene amplifications, and microsatellite instability in ffpe tumor material
title_auth	Comprehensive routine diagnostic screening to identify predictive mutations, gene amplifications, and microsatellite instability in FFPE tumor material
abstract	Background Sensitive and reliable molecular diagnostics is needed to guide therapeutic decisions for cancer patients. Although less material becomes available for testing, genetic markers are rapidly expanding. Simultaneous detection of predictive markers, including mutations, gene amplifications and MSI, will save valuable material, time and costs. Methods Using a single-molecule molecular inversion probe (smMIP)-based targeted next-generation sequencing (NGS) approach, we developed an NGS panel allowing detection of predictive mutations in 33 genes, gene amplifications of 13 genes and microsatellite instability (MSI) by the evaluation of 55 microsatellite markers. The panel was designed to target all clinically relevant single and multiple nucleotide mutations in routinely available lung cancer, colorectal cancer, melanoma, and gastro-intestinal stromal tumor samples, but is useful for a broader set of tumor types. Results The smMIP-based NGS panel was successfully validated and cut-off values were established for reliable gene amplification analysis (i.e. relative coverage ≥3) and MSI detection (≥30% unstable loci). After validation, 728 routine diagnostic tumor samples including a broad range of tumor types were sequenced with sufficient sensitivity (2.4% drop-out), including samples with low DNA input (< 10 ng; 88% successful), low tumor purity (5–10%; 77% successful), and cytological material (90% successful). 75% of these tumor samples showed ≥1 (likely) pathogenic mutation, including targetable mutations (e.g. EGFR, BRAF, MET, ERBB2, KIT, PDGFRA). Amplifications were observed in 5.5% of the samples, comprising clinically relevant amplifications (e.g. MET, ERBB2, FGFR1). 1.5% of the tumor samples were classified as MSI-high, including both MSI-prone and non-MSI-prone tumors. Conclusions We developed a comprehensive workflow for predictive analysis of diagnostic tumor samples. The smMIP-based NGS analysis was shown suitable for limited amounts of histological and cytological material. As smMIP technology allows easy adaptation of panels, this approach can comply with the rapidly expanding molecular markers.
abstractGer	Background Sensitive and reliable molecular diagnostics is needed to guide therapeutic decisions for cancer patients. Although less material becomes available for testing, genetic markers are rapidly expanding. Simultaneous detection of predictive markers, including mutations, gene amplifications and MSI, will save valuable material, time and costs. Methods Using a single-molecule molecular inversion probe (smMIP)-based targeted next-generation sequencing (NGS) approach, we developed an NGS panel allowing detection of predictive mutations in 33 genes, gene amplifications of 13 genes and microsatellite instability (MSI) by the evaluation of 55 microsatellite markers. The panel was designed to target all clinically relevant single and multiple nucleotide mutations in routinely available lung cancer, colorectal cancer, melanoma, and gastro-intestinal stromal tumor samples, but is useful for a broader set of tumor types. Results The smMIP-based NGS panel was successfully validated and cut-off values were established for reliable gene amplification analysis (i.e. relative coverage ≥3) and MSI detection (≥30% unstable loci). After validation, 728 routine diagnostic tumor samples including a broad range of tumor types were sequenced with sufficient sensitivity (2.4% drop-out), including samples with low DNA input (< 10 ng; 88% successful), low tumor purity (5–10%; 77% successful), and cytological material (90% successful). 75% of these tumor samples showed ≥1 (likely) pathogenic mutation, including targetable mutations (e.g. EGFR, BRAF, MET, ERBB2, KIT, PDGFRA). Amplifications were observed in 5.5% of the samples, comprising clinically relevant amplifications (e.g. MET, ERBB2, FGFR1). 1.5% of the tumor samples were classified as MSI-high, including both MSI-prone and non-MSI-prone tumors. Conclusions We developed a comprehensive workflow for predictive analysis of diagnostic tumor samples. The smMIP-based NGS analysis was shown suitable for limited amounts of histological and cytological material. As smMIP technology allows easy adaptation of panels, this approach can comply with the rapidly expanding molecular markers.
abstract_unstemmed	Background Sensitive and reliable molecular diagnostics is needed to guide therapeutic decisions for cancer patients. Although less material becomes available for testing, genetic markers are rapidly expanding. Simultaneous detection of predictive markers, including mutations, gene amplifications and MSI, will save valuable material, time and costs. Methods Using a single-molecule molecular inversion probe (smMIP)-based targeted next-generation sequencing (NGS) approach, we developed an NGS panel allowing detection of predictive mutations in 33 genes, gene amplifications of 13 genes and microsatellite instability (MSI) by the evaluation of 55 microsatellite markers. The panel was designed to target all clinically relevant single and multiple nucleotide mutations in routinely available lung cancer, colorectal cancer, melanoma, and gastro-intestinal stromal tumor samples, but is useful for a broader set of tumor types. Results The smMIP-based NGS panel was successfully validated and cut-off values were established for reliable gene amplification analysis (i.e. relative coverage ≥3) and MSI detection (≥30% unstable loci). After validation, 728 routine diagnostic tumor samples including a broad range of tumor types were sequenced with sufficient sensitivity (2.4% drop-out), including samples with low DNA input (< 10 ng; 88% successful), low tumor purity (5–10%; 77% successful), and cytological material (90% successful). 75% of these tumor samples showed ≥1 (likely) pathogenic mutation, including targetable mutations (e.g. EGFR, BRAF, MET, ERBB2, KIT, PDGFRA). Amplifications were observed in 5.5% of the samples, comprising clinically relevant amplifications (e.g. MET, ERBB2, FGFR1). 1.5% of the tumor samples were classified as MSI-high, including both MSI-prone and non-MSI-prone tumors. Conclusions We developed a comprehensive workflow for predictive analysis of diagnostic tumor samples. The smMIP-based NGS analysis was shown suitable for limited amounts of histological and cytological material. As smMIP technology allows easy adaptation of panels, this approach can comply with the rapidly expanding molecular markers.
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title_short	Comprehensive routine diagnostic screening to identify predictive mutations, gene amplifications, and microsatellite instability in FFPE tumor material
url	https://dx.doi.org/10.1186/s12885-020-06785-6
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author2	Kroeze, Leonie I. Tops, Bastiaan B. J. van Kempen, Leon C. ter Elst, Arja Kastner-van Raaij, Annemiek W. M. Hendriks-Cornelissen, Sandra J. B. Hermsen, Mandy J. W. Jansen, Erik A. M. Nederlof, Petra M. Schuuring, Ed Ligtenberg, Marjolijn J. L. Eijkelenboom, Astrid
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up_date	2024-07-03T23:28:08.933Z
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fullrecord_marcxml	<?xml version="1.0" encoding="UTF-8"?><collection xmlns="http://www.loc.gov/MARC21/slim"><record><leader>01000caa a22002652 4500</leader><controlfield tag="001">SPR039348423</controlfield><controlfield tag="003">DE-627</controlfield><controlfield tag="005">20230519161838.0</controlfield><controlfield tag="007">cr uuu---uuuuu</controlfield><controlfield tag="008">201007s2020 xx \|\|\|\|\|o 00\| \|\|eng c</controlfield><datafield tag="024" ind1="7" ind2=" "><subfield code="a">10.1186/s12885-020-06785-6</subfield><subfield code="2">doi</subfield></datafield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(DE-627)SPR039348423</subfield></datafield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(SPR)s12885-020-06785-6-e</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="082" ind1="0" ind2="4"><subfield code="a">610</subfield><subfield code="q">ASE</subfield></datafield><datafield tag="084" ind1=" " ind2=" "><subfield code="a">44.00</subfield><subfield code="2">bkl</subfield></datafield><datafield tag="100" ind1="1" ind2=" "><subfield code="a">Steeghs, Elisabeth M. P.</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="245" ind1="1" ind2="0"><subfield code="a">Comprehensive routine diagnostic screening to identify predictive mutations, gene amplifications, and microsatellite instability in FFPE tumor material</subfield></datafield><datafield tag="264" ind1=" " ind2="1"><subfield code="c">2020</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">Background Sensitive and reliable molecular diagnostics is needed to guide therapeutic decisions for cancer patients. Although less material becomes available for testing, genetic markers are rapidly expanding. Simultaneous detection of predictive markers, including mutations, gene amplifications and MSI, will save valuable material, time and costs. Methods Using a single-molecule molecular inversion probe (smMIP)-based targeted next-generation sequencing (NGS) approach, we developed an NGS panel allowing detection of predictive mutations in 33 genes, gene amplifications of 13 genes and microsatellite instability (MSI) by the evaluation of 55 microsatellite markers. The panel was designed to target all clinically relevant single and multiple nucleotide mutations in routinely available lung cancer, colorectal cancer, melanoma, and gastro-intestinal stromal tumor samples, but is useful for a broader set of tumor types. Results The smMIP-based NGS panel was successfully validated and cut-off values were established for reliable gene amplification analysis (i.e. relative coverage ≥3) and MSI detection (≥30% unstable loci). After validation, 728 routine diagnostic tumor samples including a broad range of tumor types were sequenced with sufficient sensitivity (2.4% drop-out), including samples with low DNA input (< 10 ng; 88% successful), low tumor purity (5–10%; 77% successful), and cytological material (90% successful). 75% of these tumor samples showed ≥1 (likely) pathogenic mutation, including targetable mutations (e.g. EGFR, BRAF, MET, ERBB2, KIT, PDGFRA). Amplifications were observed in 5.5% of the samples, comprising clinically relevant amplifications (e.g. MET, ERBB2, FGFR1). 1.5% of the tumor samples were classified as MSI-high, including both MSI-prone and non-MSI-prone tumors. Conclusions We developed a comprehensive workflow for predictive analysis of diagnostic tumor samples. The smMIP-based NGS analysis was shown suitable for limited amounts of histological and cytological material. 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Comprehensive routine diagnostic screening to identify predictive mutations, gene amplifications, and microsatellite instability in FFPE tumor material

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