Author
Listed:
- 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
Abstract
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.
Suggested Citation
Stéphanie Cornen & Arnaud Guille & José Adélaïde & Lynda Addou-Klouche & Pascal Finetti & Marie-Rose Saade & Marwa Manai & Nadine Carbuccia & Ismahane Bekhouche & Anne Letessier & Stéphane Raynaud & E, 2014.
"Candidate Luminal B Breast Cancer Genes Identified by Genome, Gene Expression and DNA Methylation Profiling,"
PLOS ONE, Public Library of Science, vol. 9(1), pages 1-16, January.
Handle:
RePEc:plo:pone00:0081843
DOI: 10.1371/journal.pone.0081843
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