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Article Dans Une Revue PLoS ONE Année : 2014

Candidate Luminal B Breast Cancer Genes Identified by Genome, Gene Expression and DNA Methylation Profiling

Stéphanie Cornen
  • Fonction : Auteur
Lynda Addou-Klouche
  • Fonction : Auteur
Marie-Rose Saade
  • Fonction : Auteur
Marwa Manai
  • Fonction : Auteur
Ismahane Bekhouche
  • Fonction : Auteur
Anne Letessier
  • Fonction : Auteur
Stéphane Raynaud
  • Fonction : Auteur
Emmanuelle Charafe-Jauffret
Hugues De The
  • Fonction : Auteur
Patrice Viens
  • Fonction : Auteur
François Bertucci
Daniel Birnbaum
  • Fonction : Auteur
  • PersonId : 834190
Max Chaffanet

Résumé

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.
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hal-01614950 , version 1 (01-10-2018)

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Stéphanie Cornen, Arnaud Guille, José Adelaïde, Lynda Addou-Klouche, Pascal Finetti, et al.. Candidate Luminal B Breast Cancer Genes Identified by Genome, Gene Expression and DNA Methylation Profiling. PLoS ONE, 2014, 9 (1), pp.e81843. ⟨10.1371/journal.pone.0081843⟩. ⟨hal-01614950⟩

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