Personalized genomic analyses for cancer mutation discovery and interpretation

摘要: Massively parallel sequencing approaches are beginning to be used clinically characterize individual patient tumors and select therapies based on the identified mutations. A major question in these analyses is extent which methods identify actionable alterations whether examination of tumor tissue alone sufficient or matched normal DNA should also analyzed accurately tumor-specific (somatic) alterations. To address issues, we comprehensively evaluated 815 tumor-normal paired samples from patients 15 types. We genomic using next-generation whole exomes 111 targeted genes that were validated with sensitivities >95% >99%, respectively, specificities >99.99%. These revealed an average 140 4.3 somatic mutations per exome analysis, respectively. More than 75% cases had associated known current clinical trials. Analyses germline cancer-predisposing 3% apparently sporadic cancers. In contrast, a tumor-only approach could not definitively changes led additional false-positive findings comprising 31% 65% analyses, including potentially genes. data suggest essential for precise identification interpretation have important implications diagnostic therapeutic management cancer patients.