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 Discovjournal_title
Cancer discoveryauthors
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 Kdoi
10.1158/2159-8290.CD-11-0325subject
Has Abstractpub_date
2012-06-01 00:00:00pages
503-11issue
6eissn
2159-8274issn
2159-8290pii
2159-8290.CD-11-0325journal_volume
2pub_type
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