Copy number and targeted mutational analysis reveals novel somatic events in metastatic prostate tumors

作者: Christiane M Robbins , Waibov A Tembe , Angela Baker , Shripad Sinari , Tracy Y Moses

DOI: 10.1101/GR.107961.110

关键词: BiologyDNA Mutational AnalysisPTENGeneticsCopy number analysisProstate cancerPoint mutationGene dosageSomatic cellComparative genomic hybridization

摘要: Advanced prostate cancer can progress to systemic metastatic tumors, which are generally androgen insensitive and ultimately lethal. Here, we report a comprehensive genomic survey for somatic events in tumors using both high-resolution copy number analysis targeted mutational of 3508 exons from 577 cancer-related genes next generation sequencing. Focal homozygous deletions were detected at 8p22, 10q23.31, 13q13.1, 13q14.11, 13q14.12. Key mapping within these deleted regions include PTEN, BRCA2, C13ORF15, SIAH3. high-level amplifications 5p13.2-p12, 14q21.1, 7q22.1, Xq12. amplified SKP2, FOXA1, AR. Furthermore, normal-tumor pairs has identified mutations known be associated with including AR TP53, but also revealed novel point MTOR, ARHGEF12, CHD5. Finally, one patient where multiple independent available, show common divergent alterations that occur the mutation level, supporting model clonal progenitor tumor-specific divergence. Our study represents deep advanced candidate alterations, possibly contributing lethal cancer.

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