Personalized oncogenomics in the management of gastrointestinal carcinomas-early experiences from a pilot study.
| Authors | B S Sheffield, B Tessier-Cloutier, H Li-Chang, Y Shen, E Pleasance, K Kasaian, Y Li, S J M Jones, H J Lim, D J Renouf, D G Huntsman, S Yip, J Laskin, M Marra & D F Schaeffer |
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| Abstract | Background 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. Methods 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. Results 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. Summary We show that whole-genome and transcriptome sequencing can be achieved within clinically effective timelines, yielding clinically useful and actionable information. Keywords: Oncogenomics, genomics, cholangiocarcinoma, colonic adenocarcinoma, appendiceal adenocarcinoma, targeted therapy, personalized medicine, bevacizumab |
| Journal Name and Citation | Curr Oncol. 2016 Dec;23(6):e571-e575. doi: 10.3747/co.23.3165. Epub 2016 Dec 21. |
| Date of Publication | 2016/12/23 |
| Publication Link | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5176383/ |