1. Personalized oncogenomics in the management of gastrointestinal carcinomas&mdash
- Author
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Sheffield, B.S., Tessier-Cloutier, B., Li-Chang, H., Shen, Y., Pleasance, E., Kasaian, K., Li, Y., Jones, S.J.M., Lim, H.J., Renouf, D.J., Huntsman, D.G., Yip, S., Laskin, J., Marra, M., and Schaeffer, D.F.
- Subjects
Oncogenomics ,colonic adenocarcinoma ,appendiceal adenocarcinoma ,genomics ,personalized medicine ,bevacizumab ,cholangiocarcinoma ,targeted therapy ,digestive system diseases - Abstract
Gastrointestinal carcinomas are genomically complex cancers that are lethal in the metastatic setting. Whole-genome and transcriptome sequencing allow for the simultaneous characterization of multiple oncogenic pathways. We report 3 cases of metastatic gastrointestinal carcinoma in patients enrolled in the Personalized Onco-Genomics program at the BC Cancer Agency. Real-time genomic profiling was combined with clinical expertise to diagnose a carcinoma of unknown primary, to explore treatment response to bevacizumab in a colorectal cancer, and to characterize an appendiceal adenocarcinoma. In the first case, genomic profiling revealed an IDH1 somatic mutation, supporting the diagnosis of cholangiocarcinoma in a malignancy of unknown origin, and further guided therapy by identifying epidermal growth factor receptor amplification. In the second case, a BRAF V600E mutation and wild-type KRAS profile justified the use of targeted therapies to treat a colonic adenocarcinoma. The third case was an appendiceal adenocarcinoma defined by a p53 inactivation, Ras/raf/mek, Akt/mtor, Wnt, and notch pathway activation, and overexpression of ret, erbb2 (her2), erbb3, met, and cell cycle regulators. We show that whole-genome and transcriptome sequencing can be achieved within clinically effective timelines, yielding clinically useful and actionable information.
- Published
- 2016
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