Candidate luminal B breast cancer genes identified by genome, gene expression and DNA methylation profiling.
Breast cancers (BCs) of the luminal B subtype are estrogen receptor-positive (ER+), highly proliferative, resistant to standard therapies and have a poor prognosis. To better understand this subtype we compared DNA copy number aberrations (CNAs), DNA promoter methylation, gene expression profiles, a...
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doaj-dd7de6bb6d7f4633bb855660fd9edec52020-11-25T01:52:45ZengPublic Library of Science (PLoS)PLoS ONE1932-62032014-01-0191e8184310.1371/journal.pone.0081843Candidate luminal B breast cancer genes identified by genome, gene expression and DNA methylation profiling.Stéphanie CornenArnaud GuilleJosé AdélaïdeLynda Addou-KlouchePascal FinettiMarie-Rose SaadeMarwa ManaiNadine CarbucciaIsmahane BekhoucheAnne LetessierStéphane RaynaudEmmanuelle Charafe-JauffretJocelyne JacquemierSalvatore SpicugliaHugues de ThePatrice ViensFrançois BertucciDaniel BirnbaumMax ChaffanetBreast cancers (BCs) of the luminal B subtype are estrogen receptor-positive (ER+), highly proliferative, resistant to standard therapies and have a poor prognosis. To better understand this subtype we compared DNA copy number aberrations (CNAs), DNA promoter methylation, gene expression profiles, and somatic mutations in nine selected genes, in 32 luminal B tumors with those observed in 156 BCs of the other molecular subtypes. Frequent CNAs included 8p11-p12 and 11q13.1-q13.2 amplifications, 7q11.22-q34, 8q21.12-q24.23, 12p12.3-p13.1, 12q13.11-q24.11, 14q21.1-q23.1, 17q11.1-q25.1, 20q11.23-q13.33 gains and 6q14.1-q24.2, 9p21.3-p24,3, 9q21.2, 18p11.31-p11.32 losses. A total of 237 and 101 luminal B-specific candidate oncogenes and tumor suppressor genes (TSGs) presented a deregulated expression in relation with their CNAs, including 11 genes previously reported associated with endocrine resistance. Interestingly, 88% of the potential TSGs are located within chromosome arm 6q, and seven candidate oncogenes are potential therapeutic targets. A total of 100 candidate oncogenes were validated in a public series of 5,765 BCs and the overexpression of 67 of these was associated with poor survival in luminal tumors. Twenty-four genes presented a deregulated expression in relation with a high DNA methylation level. FOXO3, PIK3CA and TP53 were the most frequent mutated genes among the nine tested. In a meta-analysis of next-generation sequencing data in 875 BCs, KCNB2 mutations were associated with luminal B cases while candidate TSGs MDN1 (6q15) and UTRN (6q24), were mutated in this subtype. In conclusion, we have reported luminal B candidate genes that may play a role in the development and/or hormone resistance of this aggressive subtype.http://europepmc.org/articles/PMC3886975?pdf=render |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Stéphanie Cornen Arnaud Guille José Adélaïde Lynda Addou-Klouche Pascal Finetti Marie-Rose Saade Marwa Manai Nadine Carbuccia Ismahane Bekhouche Anne Letessier Stéphane Raynaud Emmanuelle Charafe-Jauffret Jocelyne Jacquemier Salvatore Spicuglia Hugues de The Patrice Viens François Bertucci Daniel Birnbaum Max Chaffanet |
spellingShingle |
Stéphanie Cornen Arnaud Guille José Adélaïde Lynda Addou-Klouche Pascal Finetti Marie-Rose Saade Marwa Manai Nadine Carbuccia Ismahane Bekhouche Anne Letessier Stéphane Raynaud Emmanuelle Charafe-Jauffret Jocelyne Jacquemier Salvatore Spicuglia Hugues de The Patrice Viens François Bertucci Daniel Birnbaum Max Chaffanet Candidate luminal B breast cancer genes identified by genome, gene expression and DNA methylation profiling. PLoS ONE |
author_facet |
Stéphanie Cornen Arnaud Guille José Adélaïde Lynda Addou-Klouche Pascal Finetti Marie-Rose Saade Marwa Manai Nadine Carbuccia Ismahane Bekhouche Anne Letessier Stéphane Raynaud Emmanuelle Charafe-Jauffret Jocelyne Jacquemier Salvatore Spicuglia Hugues de The Patrice Viens François Bertucci Daniel Birnbaum Max Chaffanet |
author_sort |
Stéphanie Cornen |
title |
Candidate luminal B breast cancer genes identified by genome, gene expression and DNA methylation profiling. |
title_short |
Candidate luminal B breast cancer genes identified by genome, gene expression and DNA methylation profiling. |
title_full |
Candidate luminal B breast cancer genes identified by genome, gene expression and DNA methylation profiling. |
title_fullStr |
Candidate luminal B breast cancer genes identified by genome, gene expression and DNA methylation profiling. |
title_full_unstemmed |
Candidate luminal B breast cancer genes identified by genome, gene expression and DNA methylation profiling. |
title_sort |
candidate luminal b breast cancer genes identified by genome, gene expression and dna methylation profiling. |
publisher |
Public Library of Science (PLoS) |
series |
PLoS ONE |
issn |
1932-6203 |
publishDate |
2014-01-01 |
description |
Breast cancers (BCs) of the luminal B subtype are estrogen receptor-positive (ER+), highly proliferative, resistant to standard therapies and have a poor prognosis. To better understand this subtype we compared DNA copy number aberrations (CNAs), DNA promoter methylation, gene expression profiles, and somatic mutations in nine selected genes, in 32 luminal B tumors with those observed in 156 BCs of the other molecular subtypes. Frequent CNAs included 8p11-p12 and 11q13.1-q13.2 amplifications, 7q11.22-q34, 8q21.12-q24.23, 12p12.3-p13.1, 12q13.11-q24.11, 14q21.1-q23.1, 17q11.1-q25.1, 20q11.23-q13.33 gains and 6q14.1-q24.2, 9p21.3-p24,3, 9q21.2, 18p11.31-p11.32 losses. A total of 237 and 101 luminal B-specific candidate oncogenes and tumor suppressor genes (TSGs) presented a deregulated expression in relation with their CNAs, including 11 genes previously reported associated with endocrine resistance. Interestingly, 88% of the potential TSGs are located within chromosome arm 6q, and seven candidate oncogenes are potential therapeutic targets. A total of 100 candidate oncogenes were validated in a public series of 5,765 BCs and the overexpression of 67 of these was associated with poor survival in luminal tumors. Twenty-four genes presented a deregulated expression in relation with a high DNA methylation level. FOXO3, PIK3CA and TP53 were the most frequent mutated genes among the nine tested. In a meta-analysis of next-generation sequencing data in 875 BCs, KCNB2 mutations were associated with luminal B cases while candidate TSGs MDN1 (6q15) and UTRN (6q24), were mutated in this subtype. In conclusion, we have reported luminal B candidate genes that may play a role in the development and/or hormone resistance of this aggressive subtype. |
url |
http://europepmc.org/articles/PMC3886975?pdf=render |
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