Evolution of an adenocarcinoma in response to selection by targeted kinase inhibitors

摘要: Adenocarcinomas of the tongue are rare and represent minority (20 to 25%) salivary gland tumors affecting tongue. We investigated utility massively parallel sequencing characterize an adenocarcinoma tongue, before after treatment. In pre-treatment tumor we identified 7,629 genes within regions copy number gain. There were 1,078 that exhibited increased expression relative blood unrelated four contained somatic protein-coding mutations. Our analysis suggested cells driven by RET oncogene. Genes whose protein products targeted inhibitors sunitinib sorafenib correlated with being amplified or highly expressed. Consistent our observations, administration was associated stable disease lasting 4 months, which lung lesions began grow. Administration sulindac provided stabilization for additional 3 months cancer progressed new appeared. A recurring metastasis possessed 7,288 amplicons, 385 exhibiting other 9 coding The observed mutations amplifications consistent therapeutic resistance arising through activation MAPK AKT pathways. conclude complete genomic characterization a has potential aid in clinical decision making identifying approaches where no established treatment protocols exist. These results also provide direct vivo evidence mutational evolution under drug selection mechanisms accrual.