Abstract 1119: Subclonal structure of breast cancer subtypes determined by quantitative analyses of activating mutations

Little is known about the role of low-frequency somatic mutations in breast cancer, a cancer that is quite variable in terms of clinical features, prognosis and response to treatment. Because undetected mutant subpopulations have the potential to cause resistance to molecularly-targeted cancer therapies, this study investigated whether different subtypes of ductal carcinomas (DCs) encompass subpopulations of cells with cancer-driver mutations known to impact response to targeted therapies. Using the sensitive and quantitative ACB-PCR approach PIK3CA H1047R and BRAF V600E point mutations were quantified in 82 DCs, consisting of ER/PR+/HER2- (n = 20), ER/PR+/HER2+ (n = 20), ER/PR-/HER2+ (n = 21), and ER/PR-/HER2- (TNBC; n = 21) subtypes. Considering all subtypes together, the geometric mean mutant fraction (MF) measurements [provided along with (5th to 95th percentiles)] were: PIK3CA H1047R, 6.8 × 10−6 (2.5 × 10−8 to 6.3 × 10−2) and BRAF V600E, 1.9 × 10−5 (5.1 × 10−6 to 1.6 × 10−4). The PIK3CA H1047R and BRAF V600E mutations were detected (i.e., had MFs > 10−5) in 41% and 37% of DCs, respectively. In addition, normal breast tissues were analyzed by ACB-PCR to define the background levels of these mutations. For normal breast (n = 10), the geometric mean MF measurements [provided along with (5th to 95th percentiles)] were: PIK3CA H1047R, 8.0 × 10−4 (1.6 × 10−5 to 3.8 × 10−2) and BRAF V600E, 2.0 × 10−6 (9.7 × 10−7 to 1.7 × 10−4). DC subtype a...
Source: Cancer Research - Category: Cancer & Oncology Authors: Tags: Molecular and Cellular Biology Source Type: research