Intertumor heterogeneity of non-small-cell lung carcinomas revealed by multiplexed mutation profiling and integrative genomics.

摘要: Non-small-cell lung cancer (NSCLC) is a heterogeneous disease, with burden of genomic alterations exceeding most other tumors. The goal our study was to evaluate the frequencies co-occurring mutations and copy-number aberrations (CNAs) within same tumor their potential clinical impact. Mass-spectrometry based mutation profiling using customized panel evaluating 214 across 26 key NSCLC genes performed on 230 nonsquamous integrated genome-wide CNAs variables. Among 138 cases having at least one mutation, one-third (41, 29.7%) showed two or more mutations, either in gene (double mutation) different (co-mutations). In epidermal growth factor receptor (EGFR) mutant cancers, there double 18% co-mutations following genes: TP53 (10%), PIK3CA (8%), STK11 (6%) MET (4%). Significant relationships were detected between EGFR 1p, 7p copy gains (harboring gene) as well 13q loss. KRAS significantly related 1q gain 3q For Stage I, tumors harboring correlated poor prognosis (p-value = 0.02). When combining mutational status, patients both highest CNA (3q22.3 loss) significant poorer (p-value = 0.03). Our highlights relevance studying complexity by integrative analysis need for developing assays that broadly screen “actionable” improve precision stratified treatment approaches.