Open AccessPersonalized Oncogenomics in the Management of Gastrointestinal Carcinomas—Early Experiences from a Pilot Study
Author(s) -
Brandon S. Sheffield,
Basile TessierCloutier,
Hector Li-Chang,
Yaoqing Shen,
Erin Pleasance,
Katayoon Kasaian,
Y Li,
Steve Jones,
Howard John Lim,
Daniel J. Renouf,
David G. Huntsman,
Stephen Yip,
Janessa Laskin,
Marco A. Marra,
David F. Schaeffer
Publication year - 2016
Publication title -
current oncology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.053
H-Index - 51
eISSN - 1718-7729
pISSN - 1198-0052
DOI - 10.3747/co.23.3165
Subject(s) - kras , medicine , targeted therapy , adenocarcinoma , colorectal cancer , cancer research , bevacizumab , transcriptome , cancer , oncology , bioinformatics , biology , gene , genetics , chemotherapy , gene expression
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. We show that whole-genome and transcriptome sequencing can be achieved within clinically effective timelines, yielding clinically useful and actionable information.