Evolutionary pathways in BRCA1-associated breast tumors.

Abstract:

:BRCA1-associated breast tumors display loss of BRCA1 and frequent somatic mutations of PTEN and TP53. Here we describe the analysis of BRCA1, PTEN, and p53 at the single cell level in 55 BRCA1-associated breast tumors and computational methods to predict the relative temporal order of somatic events, on the basis of the frequency of cells with single or combined alterations. Although there is no obligatory order of events, we found that loss of PTEN is the most common first event and is associated with basal-like subtype, whereas in the majority of luminal tumors, mutation of TP53 occurs first and mutant PIK3CA is rarely detected. We also observed intratumor heterogeneity for the loss of wild-type BRCA1 and increased cell proliferation and centrosome amplification in the normal breast epithelium of BRCA1 mutation carriers. Our results have important implications for the design of chemopreventive and therapeutic interventions in this high-risk patient population.

journal_name

Cancer Discov

journal_title

Cancer discovery

authors

Martins FC,De S,Almendro V,Gönen M,Park SY,Blum JL,Herlihy W,Ethington G,Schnitt SJ,Tung N,Garber JE,Fetten K,Michor F,Polyak K

doi

10.1158/2159-8290.CD-11-0325

subject

Has Abstract

pub_date

2012-06-01 00:00:00

pages

503-11

issue

6

eissn

2159-8274

issn

2159-8290

pii

2159-8290.CD-11-0325

journal_volume

2

pub_type

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