Whole genome methylation profiles as independent markers of survival in stage IIIC melanoma patients

<p<Abstract</p< <p<Background</p< <p<The clinical course of cutaneous melanoma (CM) can differ significantly for patients with identical stages of disease, defined clinico-pathologically, and no molecular markers differentiate patients with such a diverse prognosis. This study aimed to define the prognostic value of whole genome DNA methylation profiles in stage III CM.</p< <p<Methods</p< <p<Genome-wide methylation profiles were evaluated by the Illumina Human Methylation 27 BeadChip assay in short-term neoplastic cell cultures from 45 stage IIIC CM patients. Unsupervised K-means partitioning clustering was exploited to sort patients into 2 groups based on their methylation profiles. Methylation patterns related to the discovered groups were determined using the nearest shrunken centroid classification algorithm. The impact of genome-wide methylation patterns on overall survival (OS) was assessed using Cox regression and Kaplan-Meier analyses.</p< <p<Results</p< <p<Unsupervised K-means partitioning by whole genome methylation profiles identified classes with significantly different OS in stage IIIC CM patients. Patients with a “favorable” methylation profile had increased OS (P = 0.001, log-rank = 10.2) by Kaplan-Meier analysis. Median OS of stage IIIC patients with a “favorable” vs. “unfavorable” methylation profile were 31.5 and 10.4 months, respectively. The 5 year OS for stage IIIC patients with a “favorable” methylation profile was 41.2% as compared to 0% for patients with an “unfavorable” methylation profile. Among the variables examined by multivariate Cox regression analysis, classification defined by methylation profile was the only predictor of OS (Hazard Ratio = 2.41, for “unfavorable” methylation profile; 95% Confidence Interval: 1.02-5.70; <it<P</it< = 0.045). A 17 gene methylation signature able to correctly assign prognosis (overall error rate = 0) in stage IIIC patients on the basis of distinct methylation-defined groups was also identified.</p< <p<Conclusions</p< <p<A discrete whole-genome methylation signature has been identified as molecular marker of prognosis for stage IIIC CM patients. Its use in daily practice is foreseeable, and promises to refine the comprehensive clinical management of stage III CM patients.</p< Ausführliche Beschreibung

Gespeichert in:

Autor*in:	Sigalotti Luca [verfasserIn] Covre Alessia [verfasserIn] Fratta Elisabetta [verfasserIn] Parisi Giulia [verfasserIn] Sonego Paolo [verfasserIn] Colizzi Francesca [verfasserIn] Coral Sandra [verfasserIn] Massarut Samuele [verfasserIn] Kirkwood John M [verfasserIn] Maio Michele [verfasserIn]

Format:	E-Artikel
Sprache:	Englisch

Erschienen:	2012

Schlagwörter:	Whole-genome methylation profiling Prognosis Prognostic signature Hypermethylation Immunotherapy

Übergeordnetes Werk:	In: Journal of Translational Medicine - BMC, 2003, 10(2012), 1, p 185
Übergeordnetes Werk:	volume:10 ; year:2012 ; number:1, p 185

Links:	Link aufrufen Link aufrufen Link aufrufen Journal toc

DOI / URN:	10.1186/1479-5876-10-185

Katalog-ID:	DOAJ066010225

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allfields	10.1186/1479-5876-10-185 doi (DE-627)DOAJ066010225 (DE-599)DOAJad91512dc0e64a1c92b8873c7bbe3573 DE-627 ger DE-627 rakwb eng Sigalotti Luca verfasserin aut Whole genome methylation profiles as independent markers of survival in stage IIIC melanoma patients 2012 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier <p<Abstract</p< <p<Background</p< <p<The clinical course of cutaneous melanoma (CM) can differ significantly for patients with identical stages of disease, defined clinico-pathologically, and no molecular markers differentiate patients with such a diverse prognosis. This study aimed to define the prognostic value of whole genome DNA methylation profiles in stage III CM.</p< <p<Methods</p< <p<Genome-wide methylation profiles were evaluated by the Illumina Human Methylation 27 BeadChip assay in short-term neoplastic cell cultures from 45 stage IIIC CM patients. Unsupervised K-means partitioning clustering was exploited to sort patients into 2 groups based on their methylation profiles. Methylation patterns related to the discovered groups were determined using the nearest shrunken centroid classification algorithm. The impact of genome-wide methylation patterns on overall survival (OS) was assessed using Cox regression and Kaplan-Meier analyses.</p< <p<Results</p< <p<Unsupervised K-means partitioning by whole genome methylation profiles identified classes with significantly different OS in stage IIIC CM patients. Patients with a “favorable” methylation profile had increased OS (P = 0.001, log-rank = 10.2) by Kaplan-Meier analysis. Median OS of stage IIIC patients with a “favorable” vs. “unfavorable” methylation profile were 31.5 and 10.4 months, respectively. The 5 year OS for stage IIIC patients with a “favorable” methylation profile was 41.2% as compared to 0% for patients with an “unfavorable” methylation profile. Among the variables examined by multivariate Cox regression analysis, classification defined by methylation profile was the only predictor of OS (Hazard Ratio = 2.41, for “unfavorable” methylation profile; 95% Confidence Interval: 1.02-5.70; <it<P</it< = 0.045). A 17 gene methylation signature able to correctly assign prognosis (overall error rate = 0) in stage IIIC patients on the basis of distinct methylation-defined groups was also identified.</p< <p<Conclusions</p< <p<A discrete whole-genome methylation signature has been identified as molecular marker of prognosis for stage IIIC CM patients. Its use in daily practice is foreseeable, and promises to refine the comprehensive clinical management of stage III CM patients.</p< Whole-genome methylation profiling Prognosis Prognostic signature Hypermethylation Immunotherapy Medicine R Covre Alessia verfasserin aut Fratta Elisabetta verfasserin aut Parisi Giulia verfasserin aut Sonego Paolo verfasserin aut Colizzi Francesca verfasserin aut Coral Sandra verfasserin aut Massarut Samuele verfasserin aut Kirkwood John M verfasserin aut Maio Michele verfasserin aut In Journal of Translational Medicine BMC, 2003 10(2012), 1, p 185 (DE-627)369084136 (DE-600)2118570-0 14795876 nnns volume:10 year:2012 number:1, p 185 https://doi.org/10.1186/1479-5876-10-185 kostenfrei https://doaj.org/article/ad91512dc0e64a1c92b8873c7bbe3573 kostenfrei http://www.translational-medicine.com/content/10/1/185 kostenfrei https://doaj.org/toc/1479-5876 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_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_2003 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 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 AR 10 2012 1, p 185
spelling	10.1186/1479-5876-10-185 doi (DE-627)DOAJ066010225 (DE-599)DOAJad91512dc0e64a1c92b8873c7bbe3573 DE-627 ger DE-627 rakwb eng Sigalotti Luca verfasserin aut Whole genome methylation profiles as independent markers of survival in stage IIIC melanoma patients 2012 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier <p<Abstract</p< <p<Background</p< <p<The clinical course of cutaneous melanoma (CM) can differ significantly for patients with identical stages of disease, defined clinico-pathologically, and no molecular markers differentiate patients with such a diverse prognosis. This study aimed to define the prognostic value of whole genome DNA methylation profiles in stage III CM.</p< <p<Methods</p< <p<Genome-wide methylation profiles were evaluated by the Illumina Human Methylation 27 BeadChip assay in short-term neoplastic cell cultures from 45 stage IIIC CM patients. Unsupervised K-means partitioning clustering was exploited to sort patients into 2 groups based on their methylation profiles. Methylation patterns related to the discovered groups were determined using the nearest shrunken centroid classification algorithm. The impact of genome-wide methylation patterns on overall survival (OS) was assessed using Cox regression and Kaplan-Meier analyses.</p< <p<Results</p< <p<Unsupervised K-means partitioning by whole genome methylation profiles identified classes with significantly different OS in stage IIIC CM patients. Patients with a “favorable” methylation profile had increased OS (P = 0.001, log-rank = 10.2) by Kaplan-Meier analysis. Median OS of stage IIIC patients with a “favorable” vs. “unfavorable” methylation profile were 31.5 and 10.4 months, respectively. The 5 year OS for stage IIIC patients with a “favorable” methylation profile was 41.2% as compared to 0% for patients with an “unfavorable” methylation profile. Among the variables examined by multivariate Cox regression analysis, classification defined by methylation profile was the only predictor of OS (Hazard Ratio = 2.41, for “unfavorable” methylation profile; 95% Confidence Interval: 1.02-5.70; <it<P</it< = 0.045). A 17 gene methylation signature able to correctly assign prognosis (overall error rate = 0) in stage IIIC patients on the basis of distinct methylation-defined groups was also identified.</p< <p<Conclusions</p< <p<A discrete whole-genome methylation signature has been identified as molecular marker of prognosis for stage IIIC CM patients. Its use in daily practice is foreseeable, and promises to refine the comprehensive clinical management of stage III CM patients.</p< Whole-genome methylation profiling Prognosis Prognostic signature Hypermethylation Immunotherapy Medicine R Covre Alessia verfasserin aut Fratta Elisabetta verfasserin aut Parisi Giulia verfasserin aut Sonego Paolo verfasserin aut Colizzi Francesca verfasserin aut Coral Sandra verfasserin aut Massarut Samuele verfasserin aut Kirkwood John M verfasserin aut Maio Michele verfasserin aut In Journal of Translational Medicine BMC, 2003 10(2012), 1, p 185 (DE-627)369084136 (DE-600)2118570-0 14795876 nnns volume:10 year:2012 number:1, p 185 https://doi.org/10.1186/1479-5876-10-185 kostenfrei https://doaj.org/article/ad91512dc0e64a1c92b8873c7bbe3573 kostenfrei http://www.translational-medicine.com/content/10/1/185 kostenfrei https://doaj.org/toc/1479-5876 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_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_2003 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 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 AR 10 2012 1, p 185
allfields_unstemmed	10.1186/1479-5876-10-185 doi (DE-627)DOAJ066010225 (DE-599)DOAJad91512dc0e64a1c92b8873c7bbe3573 DE-627 ger DE-627 rakwb eng Sigalotti Luca verfasserin aut Whole genome methylation profiles as independent markers of survival in stage IIIC melanoma patients 2012 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier <p<Abstract</p< <p<Background</p< <p<The clinical course of cutaneous melanoma (CM) can differ significantly for patients with identical stages of disease, defined clinico-pathologically, and no molecular markers differentiate patients with such a diverse prognosis. This study aimed to define the prognostic value of whole genome DNA methylation profiles in stage III CM.</p< <p<Methods</p< <p<Genome-wide methylation profiles were evaluated by the Illumina Human Methylation 27 BeadChip assay in short-term neoplastic cell cultures from 45 stage IIIC CM patients. Unsupervised K-means partitioning clustering was exploited to sort patients into 2 groups based on their methylation profiles. Methylation patterns related to the discovered groups were determined using the nearest shrunken centroid classification algorithm. The impact of genome-wide methylation patterns on overall survival (OS) was assessed using Cox regression and Kaplan-Meier analyses.</p< <p<Results</p< <p<Unsupervised K-means partitioning by whole genome methylation profiles identified classes with significantly different OS in stage IIIC CM patients. Patients with a “favorable” methylation profile had increased OS (P = 0.001, log-rank = 10.2) by Kaplan-Meier analysis. Median OS of stage IIIC patients with a “favorable” vs. “unfavorable” methylation profile were 31.5 and 10.4 months, respectively. The 5 year OS for stage IIIC patients with a “favorable” methylation profile was 41.2% as compared to 0% for patients with an “unfavorable” methylation profile. Among the variables examined by multivariate Cox regression analysis, classification defined by methylation profile was the only predictor of OS (Hazard Ratio = 2.41, for “unfavorable” methylation profile; 95% Confidence Interval: 1.02-5.70; <it<P</it< = 0.045). A 17 gene methylation signature able to correctly assign prognosis (overall error rate = 0) in stage IIIC patients on the basis of distinct methylation-defined groups was also identified.</p< <p<Conclusions</p< <p<A discrete whole-genome methylation signature has been identified as molecular marker of prognosis for stage IIIC CM patients. Its use in daily practice is foreseeable, and promises to refine the comprehensive clinical management of stage III CM patients.</p< Whole-genome methylation profiling Prognosis Prognostic signature Hypermethylation Immunotherapy Medicine R Covre Alessia verfasserin aut Fratta Elisabetta verfasserin aut Parisi Giulia verfasserin aut Sonego Paolo verfasserin aut Colizzi Francesca verfasserin aut Coral Sandra verfasserin aut Massarut Samuele verfasserin aut Kirkwood John M verfasserin aut Maio Michele verfasserin aut In Journal of Translational Medicine BMC, 2003 10(2012), 1, p 185 (DE-627)369084136 (DE-600)2118570-0 14795876 nnns volume:10 year:2012 number:1, p 185 https://doi.org/10.1186/1479-5876-10-185 kostenfrei https://doaj.org/article/ad91512dc0e64a1c92b8873c7bbe3573 kostenfrei http://www.translational-medicine.com/content/10/1/185 kostenfrei https://doaj.org/toc/1479-5876 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_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_2003 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 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 AR 10 2012 1, p 185
allfieldsGer	10.1186/1479-5876-10-185 doi (DE-627)DOAJ066010225 (DE-599)DOAJad91512dc0e64a1c92b8873c7bbe3573 DE-627 ger DE-627 rakwb eng Sigalotti Luca verfasserin aut Whole genome methylation profiles as independent markers of survival in stage IIIC melanoma patients 2012 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier <p<Abstract</p< <p<Background</p< <p<The clinical course of cutaneous melanoma (CM) can differ significantly for patients with identical stages of disease, defined clinico-pathologically, and no molecular markers differentiate patients with such a diverse prognosis. This study aimed to define the prognostic value of whole genome DNA methylation profiles in stage III CM.</p< <p<Methods</p< <p<Genome-wide methylation profiles were evaluated by the Illumina Human Methylation 27 BeadChip assay in short-term neoplastic cell cultures from 45 stage IIIC CM patients. Unsupervised K-means partitioning clustering was exploited to sort patients into 2 groups based on their methylation profiles. Methylation patterns related to the discovered groups were determined using the nearest shrunken centroid classification algorithm. The impact of genome-wide methylation patterns on overall survival (OS) was assessed using Cox regression and Kaplan-Meier analyses.</p< <p<Results</p< <p<Unsupervised K-means partitioning by whole genome methylation profiles identified classes with significantly different OS in stage IIIC CM patients. Patients with a “favorable” methylation profile had increased OS (P = 0.001, log-rank = 10.2) by Kaplan-Meier analysis. Median OS of stage IIIC patients with a “favorable” vs. “unfavorable” methylation profile were 31.5 and 10.4 months, respectively. The 5 year OS for stage IIIC patients with a “favorable” methylation profile was 41.2% as compared to 0% for patients with an “unfavorable” methylation profile. Among the variables examined by multivariate Cox regression analysis, classification defined by methylation profile was the only predictor of OS (Hazard Ratio = 2.41, for “unfavorable” methylation profile; 95% Confidence Interval: 1.02-5.70; <it<P</it< = 0.045). A 17 gene methylation signature able to correctly assign prognosis (overall error rate = 0) in stage IIIC patients on the basis of distinct methylation-defined groups was also identified.</p< <p<Conclusions</p< <p<A discrete whole-genome methylation signature has been identified as molecular marker of prognosis for stage IIIC CM patients. Its use in daily practice is foreseeable, and promises to refine the comprehensive clinical management of stage III CM patients.</p< Whole-genome methylation profiling Prognosis Prognostic signature Hypermethylation Immunotherapy Medicine R Covre Alessia verfasserin aut Fratta Elisabetta verfasserin aut Parisi Giulia verfasserin aut Sonego Paolo verfasserin aut Colizzi Francesca verfasserin aut Coral Sandra verfasserin aut Massarut Samuele verfasserin aut Kirkwood John M verfasserin aut Maio Michele verfasserin aut In Journal of Translational Medicine BMC, 2003 10(2012), 1, p 185 (DE-627)369084136 (DE-600)2118570-0 14795876 nnns volume:10 year:2012 number:1, p 185 https://doi.org/10.1186/1479-5876-10-185 kostenfrei https://doaj.org/article/ad91512dc0e64a1c92b8873c7bbe3573 kostenfrei http://www.translational-medicine.com/content/10/1/185 kostenfrei https://doaj.org/toc/1479-5876 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_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_2003 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 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 AR 10 2012 1, p 185
allfieldsSound	10.1186/1479-5876-10-185 doi (DE-627)DOAJ066010225 (DE-599)DOAJad91512dc0e64a1c92b8873c7bbe3573 DE-627 ger DE-627 rakwb eng Sigalotti Luca verfasserin aut Whole genome methylation profiles as independent markers of survival in stage IIIC melanoma patients 2012 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier <p<Abstract</p< <p<Background</p< <p<The clinical course of cutaneous melanoma (CM) can differ significantly for patients with identical stages of disease, defined clinico-pathologically, and no molecular markers differentiate patients with such a diverse prognosis. This study aimed to define the prognostic value of whole genome DNA methylation profiles in stage III CM.</p< <p<Methods</p< <p<Genome-wide methylation profiles were evaluated by the Illumina Human Methylation 27 BeadChip assay in short-term neoplastic cell cultures from 45 stage IIIC CM patients. Unsupervised K-means partitioning clustering was exploited to sort patients into 2 groups based on their methylation profiles. Methylation patterns related to the discovered groups were determined using the nearest shrunken centroid classification algorithm. The impact of genome-wide methylation patterns on overall survival (OS) was assessed using Cox regression and Kaplan-Meier analyses.</p< <p<Results</p< <p<Unsupervised K-means partitioning by whole genome methylation profiles identified classes with significantly different OS in stage IIIC CM patients. Patients with a “favorable” methylation profile had increased OS (P = 0.001, log-rank = 10.2) by Kaplan-Meier analysis. Median OS of stage IIIC patients with a “favorable” vs. “unfavorable” methylation profile were 31.5 and 10.4 months, respectively. The 5 year OS for stage IIIC patients with a “favorable” methylation profile was 41.2% as compared to 0% for patients with an “unfavorable” methylation profile. Among the variables examined by multivariate Cox regression analysis, classification defined by methylation profile was the only predictor of OS (Hazard Ratio = 2.41, for “unfavorable” methylation profile; 95% Confidence Interval: 1.02-5.70; <it<P</it< = 0.045). A 17 gene methylation signature able to correctly assign prognosis (overall error rate = 0) in stage IIIC patients on the basis of distinct methylation-defined groups was also identified.</p< <p<Conclusions</p< <p<A discrete whole-genome methylation signature has been identified as molecular marker of prognosis for stage IIIC CM patients. Its use in daily practice is foreseeable, and promises to refine the comprehensive clinical management of stage III CM patients.</p< Whole-genome methylation profiling Prognosis Prognostic signature Hypermethylation Immunotherapy Medicine R Covre Alessia verfasserin aut Fratta Elisabetta verfasserin aut Parisi Giulia verfasserin aut Sonego Paolo verfasserin aut Colizzi Francesca verfasserin aut Coral Sandra verfasserin aut Massarut Samuele verfasserin aut Kirkwood John M verfasserin aut Maio Michele verfasserin aut In Journal of Translational Medicine BMC, 2003 10(2012), 1, p 185 (DE-627)369084136 (DE-600)2118570-0 14795876 nnns volume:10 year:2012 number:1, p 185 https://doi.org/10.1186/1479-5876-10-185 kostenfrei https://doaj.org/article/ad91512dc0e64a1c92b8873c7bbe3573 kostenfrei http://www.translational-medicine.com/content/10/1/185 kostenfrei https://doaj.org/toc/1479-5876 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_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_2003 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 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 AR 10 2012 1, p 185
language	English
source	In Journal of Translational Medicine 10(2012), 1, p 185 volume:10 year:2012 number:1, p 185
sourceStr	In Journal of Translational Medicine 10(2012), 1, p 185 volume:10 year:2012 number:1, p 185
format_phy_str_mv	Article
institution	findex.gbv.de
topic_facet	Whole-genome methylation profiling Prognosis Prognostic signature Hypermethylation Immunotherapy Medicine R
isfreeaccess_bool	true
container_title	Journal of Translational Medicine
authorswithroles_txt_mv	Sigalotti Luca @@aut@@ Covre Alessia @@aut@@ Fratta Elisabetta @@aut@@ Parisi Giulia @@aut@@ Sonego Paolo @@aut@@ Colizzi Francesca @@aut@@ Coral Sandra @@aut@@ Massarut Samuele @@aut@@ Kirkwood John M @@aut@@ Maio Michele @@aut@@
publishDateDaySort_date	2012-01-01T00:00:00Z
hierarchy_top_id	369084136
id	DOAJ066010225
language_de	englisch
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author	Sigalotti Luca
spellingShingle	Sigalotti Luca misc Whole-genome methylation profiling misc Prognosis misc Prognostic signature misc Hypermethylation misc Immunotherapy misc Medicine misc R Whole genome methylation profiles as independent markers of survival in stage IIIC melanoma patients
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topic_title	Whole genome methylation profiles as independent markers of survival in stage IIIC melanoma patients Whole-genome methylation profiling Prognosis Prognostic signature Hypermethylation Immunotherapy
topic	misc Whole-genome methylation profiling misc Prognosis misc Prognostic signature misc Hypermethylation misc Immunotherapy misc Medicine misc R
topic_unstemmed	misc Whole-genome methylation profiling misc Prognosis misc Prognostic signature misc Hypermethylation misc Immunotherapy misc Medicine misc R
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title	Whole genome methylation profiles as independent markers of survival in stage IIIC melanoma patients
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title_full	Whole genome methylation profiles as independent markers of survival in stage IIIC melanoma patients
author_sort	Sigalotti Luca
journal	Journal of Translational Medicine
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author_browse	Sigalotti Luca Covre Alessia Fratta Elisabetta Parisi Giulia Sonego Paolo Colizzi Francesca Coral Sandra Massarut Samuele Kirkwood John M Maio Michele
container_volume	10
format_se	Elektronische Aufsätze
author-letter	Sigalotti Luca
doi_str_mv	10.1186/1479-5876-10-185
author2-role	verfasserin
title_sort	whole genome methylation profiles as independent markers of survival in stage iiic melanoma patients
title_auth	Whole genome methylation profiles as independent markers of survival in stage IIIC melanoma patients
abstract	<p<Abstract</p< <p<Background</p< <p<The clinical course of cutaneous melanoma (CM) can differ significantly for patients with identical stages of disease, defined clinico-pathologically, and no molecular markers differentiate patients with such a diverse prognosis. This study aimed to define the prognostic value of whole genome DNA methylation profiles in stage III CM.</p< <p<Methods</p< <p<Genome-wide methylation profiles were evaluated by the Illumina Human Methylation 27 BeadChip assay in short-term neoplastic cell cultures from 45 stage IIIC CM patients. Unsupervised K-means partitioning clustering was exploited to sort patients into 2 groups based on their methylation profiles. Methylation patterns related to the discovered groups were determined using the nearest shrunken centroid classification algorithm. The impact of genome-wide methylation patterns on overall survival (OS) was assessed using Cox regression and Kaplan-Meier analyses.</p< <p<Results</p< <p<Unsupervised K-means partitioning by whole genome methylation profiles identified classes with significantly different OS in stage IIIC CM patients. Patients with a “favorable” methylation profile had increased OS (P = 0.001, log-rank = 10.2) by Kaplan-Meier analysis. Median OS of stage IIIC patients with a “favorable” vs. “unfavorable” methylation profile were 31.5 and 10.4 months, respectively. The 5 year OS for stage IIIC patients with a “favorable” methylation profile was 41.2% as compared to 0% for patients with an “unfavorable” methylation profile. Among the variables examined by multivariate Cox regression analysis, classification defined by methylation profile was the only predictor of OS (Hazard Ratio = 2.41, for “unfavorable” methylation profile; 95% Confidence Interval: 1.02-5.70; <it<P</it< = 0.045). A 17 gene methylation signature able to correctly assign prognosis (overall error rate = 0) in stage IIIC patients on the basis of distinct methylation-defined groups was also identified.</p< <p<Conclusions</p< <p<A discrete whole-genome methylation signature has been identified as molecular marker of prognosis for stage IIIC CM patients. Its use in daily practice is foreseeable, and promises to refine the comprehensive clinical management of stage III CM patients.</p<
abstractGer	<p<Abstract</p< <p<Background</p< <p<The clinical course of cutaneous melanoma (CM) can differ significantly for patients with identical stages of disease, defined clinico-pathologically, and no molecular markers differentiate patients with such a diverse prognosis. This study aimed to define the prognostic value of whole genome DNA methylation profiles in stage III CM.</p< <p<Methods</p< <p<Genome-wide methylation profiles were evaluated by the Illumina Human Methylation 27 BeadChip assay in short-term neoplastic cell cultures from 45 stage IIIC CM patients. Unsupervised K-means partitioning clustering was exploited to sort patients into 2 groups based on their methylation profiles. Methylation patterns related to the discovered groups were determined using the nearest shrunken centroid classification algorithm. The impact of genome-wide methylation patterns on overall survival (OS) was assessed using Cox regression and Kaplan-Meier analyses.</p< <p<Results</p< <p<Unsupervised K-means partitioning by whole genome methylation profiles identified classes with significantly different OS in stage IIIC CM patients. Patients with a “favorable” methylation profile had increased OS (P = 0.001, log-rank = 10.2) by Kaplan-Meier analysis. Median OS of stage IIIC patients with a “favorable” vs. “unfavorable” methylation profile were 31.5 and 10.4 months, respectively. The 5 year OS for stage IIIC patients with a “favorable” methylation profile was 41.2% as compared to 0% for patients with an “unfavorable” methylation profile. Among the variables examined by multivariate Cox regression analysis, classification defined by methylation profile was the only predictor of OS (Hazard Ratio = 2.41, for “unfavorable” methylation profile; 95% Confidence Interval: 1.02-5.70; <it<P</it< = 0.045). A 17 gene methylation signature able to correctly assign prognosis (overall error rate = 0) in stage IIIC patients on the basis of distinct methylation-defined groups was also identified.</p< <p<Conclusions</p< <p<A discrete whole-genome methylation signature has been identified as molecular marker of prognosis for stage IIIC CM patients. Its use in daily practice is foreseeable, and promises to refine the comprehensive clinical management of stage III CM patients.</p<
abstract_unstemmed	<p<Abstract</p< <p<Background</p< <p<The clinical course of cutaneous melanoma (CM) can differ significantly for patients with identical stages of disease, defined clinico-pathologically, and no molecular markers differentiate patients with such a diverse prognosis. This study aimed to define the prognostic value of whole genome DNA methylation profiles in stage III CM.</p< <p<Methods</p< <p<Genome-wide methylation profiles were evaluated by the Illumina Human Methylation 27 BeadChip assay in short-term neoplastic cell cultures from 45 stage IIIC CM patients. Unsupervised K-means partitioning clustering was exploited to sort patients into 2 groups based on their methylation profiles. Methylation patterns related to the discovered groups were determined using the nearest shrunken centroid classification algorithm. The impact of genome-wide methylation patterns on overall survival (OS) was assessed using Cox regression and Kaplan-Meier analyses.</p< <p<Results</p< <p<Unsupervised K-means partitioning by whole genome methylation profiles identified classes with significantly different OS in stage IIIC CM patients. Patients with a “favorable” methylation profile had increased OS (P = 0.001, log-rank = 10.2) by Kaplan-Meier analysis. Median OS of stage IIIC patients with a “favorable” vs. “unfavorable” methylation profile were 31.5 and 10.4 months, respectively. The 5 year OS for stage IIIC patients with a “favorable” methylation profile was 41.2% as compared to 0% for patients with an “unfavorable” methylation profile. Among the variables examined by multivariate Cox regression analysis, classification defined by methylation profile was the only predictor of OS (Hazard Ratio = 2.41, for “unfavorable” methylation profile; 95% Confidence Interval: 1.02-5.70; <it<P</it< = 0.045). A 17 gene methylation signature able to correctly assign prognosis (overall error rate = 0) in stage IIIC patients on the basis of distinct methylation-defined groups was also identified.</p< <p<Conclusions</p< <p<A discrete whole-genome methylation signature has been identified as molecular marker of prognosis for stage IIIC CM patients. Its use in daily practice is foreseeable, and promises to refine the comprehensive clinical management of stage III CM patients.</p<
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title_short	Whole genome methylation profiles as independent markers of survival in stage IIIC melanoma patients
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Whole genome methylation profiles as independent markers of survival in stage IIIC melanoma patients

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