The molecular diversity of Luminal A breast tumors.

Détails

ID Serval
serval:BIB_C34409B2F362
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
The molecular diversity of Luminal A breast tumors.
Périodique
Breast cancer research and treatment
Auteur(s)
Ciriello G., Sinha R., Hoadley K.A., Jacobsen A.S., Reva B., Perou C.M., Sander C., Schultz N.
ISSN
1573-7217 (Electronic)
ISSN-L
0167-6806
Statut éditorial
Publié
Date de publication
10/2013
Peer-reviewed
Oui
Volume
141
Numéro
3
Pages
409-420
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Résumé
Breast cancer is a collection of diseases with distinct molecular traits, prognosis, and therapeutic options. Luminal A breast cancer is the most heterogeneous, both molecularly and clinically. Using genomic data from over 1,000 Luminal A tumors from multiple studies, we analyzed the copy number and mutational landscape of this tumor subtype. This integrated analysis revealed four major subtypes defined by distinct copy-number and mutation profiles. We identified an atypical Luminal A subtype characterized by high genomic instability, TP53 mutations, and increased Aurora kinase signaling; these genomic alterations lead to a worse clinical prognosis. Aberrations of chromosomes 1, 8, and 16, together with PIK3CA, GATA3, AKT1, and MAP3K1 mutations drive the other subtypes. Finally, an unbiased pathway analysis revealed multiple rare, but mutually exclusive, alterations linked to loss of activity of co-repressor complexes N-Cor and SMRT. These rare alterations were the most prevalent in Luminal A tumors and may predict resistance to endocrine therapy. Our work provides for a further molecular stratification of Luminal A breast tumors, with potential direct clinical implications.
Mots-clé
Breast Neoplasms/genetics, Breast Neoplasms/metabolism, Breast Neoplasms/mortality, Breast Neoplasms/pathology, Carcinoma, Ductal, Breast/genetics, Carcinoma, Ductal, Breast/metabolism, Carcinoma, Ductal, Breast/mortality, Carcinoma, Ductal, Breast/pathology, Class I Phosphatidylinositol 3-Kinases, DNA Copy Number Variations, DNA Mutational Analysis, Drug Resistance, Neoplasm, Female, GATA3 Transcription Factor/genetics, Gene Dosage, Gene Expression, Genomic Instability, Humans, Kaplan-Meier Estimate, MAP Kinase Kinase Kinase 1/genetics, Mutation, Phosphatidylinositol 3-Kinases/genetics, Prognosis, Proportional Hazards Models, Proto-Oncogene Proteins c-akt/genetics, Tumor Suppressor Protein p53/genetics
Pubmed
Web of science
Open Access
Oui
Création de la notice
06/07/2018 12:02
Dernière modification de la notice
09/05/2019 0:52
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