Journal
BREAST CANCER RESEARCH AND TREATMENT
Volume 141, Issue 3, Pages 409-420Publisher
SPRINGER
DOI: 10.1007/s10549-013-2699-3
Keywords
Luminal A breast cancer; Breast cancer genomics
Categories
Funding
- National Cancer Institute Cancer Genome Atlas Grant [U24-CA143840, U24-CA143848]
- National Resource for Network Biology Grant [P41 GM103504]
- NCI Breast SPORE program [P50-CA58223-09A1]
- Breast Cancer Research Foundation
- [SU2C-AACR-DT0209]
Ask authors/readers for more resources
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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available