Personalized oncogenomics in the management of gastrointestinal carcinomas— early experiences from a pilot study

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



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.



Oncogenomics; genomics; cholangiocarcinoma; colonic adenocarcinoma; appendiceal adenocarcinoma; targeted therapy; personalized medicine; bevacizumab

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ISSN: 1198-0052 (Print) ISSN: 1718-7729 (Online)