Mutation profiling identifies numerous rare drug targets and distinct mutation patterns in different clinical subtypes of breast cancers

摘要: The mutation pattern of breast cancer molecular subtypes is incompletely understood. purpose this study was to identify mutations in genes that may be targeted with currently available investigational drugs the three major (ER+/HER2−, HER2+, and Triple Negative). We extracted DNA from fine needle aspirations 267 stage I–III cancers. These tumor specimens typically consisted >80 % neoplastic cells. examined 28 for 163 known cancer-related nucleic acid variations by Sequenom technology. observed at least one 38 alleles corresponding 15 108 (40 %) samples, including PIK3CA (16.1 all samples), FBXW7 (8 %), BRAF (3.0 EGFR (2.6 AKT1 CTNNB1 (1.9 each), KIT KRAS (1.5 PDGFR-α (1.1 %). also checked polymorphism PHLPP2 activate AKT it found 13.5 patient samples. were more frequent estrogen receptor-positive cancers compared triple negative (TNBC) (19 vs. 8 %, p = 0.001). High frequency (28 HER2+ tumors. In TNBC, significantly ER+ tumors (13 5 0.037). performed validation mutated allele-specific PCR or direct sequencing; analyzed two different sequencing techniques showed 95–100 concordance status. conclusion, harbor type approximately 40 contained individually rare signaling pathways can potentially drugs. Simultaneous testing many a single biopsy feasible allows design prospective clinical trials could test functional importance these future.