Clinical validation of coexisting driver mutations in colorectal cancers.

摘要: Mutational profiling is recommended for selecting targeted therapy and predicting prognosis of metastatic colorectal cancer (CRC). Detection coexisting mutations within the same pathway, which are usually mutually exclusive, raises concern potential laboratory errors. In this retrospective study quality assessment a next-generation sequencing assay, we examined BRAF, KRAS, NRAS genes mitogen-activated protein kinase (MAPK) pathway PIK3CA gene phosphatidylinositol 3-kinase (mTOR) in 744 CRC specimens submitted to our clinical diagnostics laboratory. Although coexistence between MAPK mTOR pathways was observed, it rarely occurred pathway. Retrospective assessments identified false detection activating KRAS 1 specimen confirmed 2 specimens, but no RAS BRAF mutations. There were 15 CRCs with kinase-impaired mutation, including 3 may have therapeutic implications. Multiregional analysis based on different histologic features demonstrated that be present or tumor populations showed invasion adenomas by synchronous adenocarcinomas clonal origin result study, proposed an operating procedure validation unexpected Further studies warranted elucidate biological significance implications