Comprehensive profiling and quantitation of oncogenic mutations in non small-cell lung carcinoma using single molecule amplification and re-sequencing technology

摘要: Activating and resistance mutations in the tyrosine kinase domain of several oncogenes are frequently associated with non-small cell lung carcinoma (NSCLC). In this study we assessed frequency, type abundance EGFR, KRAS, BRAF, TP53 ALK tumour specimens from 184 patients early late stage disease using single molecule amplification re-sequencing technology (SMART). Based on modelling EGFR mutations, detection sensitivity SMART assay was at least 0.1%. Benchmarking mutation against gold standard ARMS-PCR assay, had a specificity 98.7% 99.0%. Amongst samples, were most prevalent (59.9%), followed by KRAS (16.9%), (12.7%), EML4-ALK fusions (6.3%) BRAF (4.2%) mutations. The types extremely heterogeneous, involving either monoclonal (51.6%) or polyclonal (12.6%) events. At clinical level, although spectrum mutation(s) unique to each patient, overall patterns advanced relatively similar. these findings, propose that personalized profiling quantitation clinically significant oncogenic will allow better classification according characteristics provide clinicians important ancillary information for treatment decision-making.