Personalized Oncogenomics in the Management of Gastrointestinal Carcinomas—Early Experiences from a Pilot Study
by
B.S. Sheffield
1,*, 
B. Tessier-Cloutier
1,
H. Li-Chang
2,
Y. Shen
3,
E. Pleasance
3,
K. Kasaian
3,
Y. Li
3,
S.J.M. Jones
3,
H.J. Lim
4,
D.J. Renouf
4,
D.G. Huntsman
1,
S. Yip
1,
J. Laskin
4,
M. Marra
3,5 and
D.F. Schaeffer
1 1
Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, BC V2S 0C2, Canada
2
Royal Victoria Regional Health Centre, Department of Pathology and Laboratory Medicine, Barrie, ON, Canada
3
Canada’s Michael Smith Genome Sciences Centre, BC Cancer Agency, Vancouver, BC, Canada
4
Division of Medical Oncology, BC Cancer Agency, Vancouver, BC, Canada
5
Department of Medical Genetics, University of British Columbia, Vancouver, BC, Canada
*
Author to whom correspondence should be addressed.
Curr. Oncol. 2016, 23(6), 571-575; https://doi.org/10.3747/co.23.3165
Submission received: 7 September 2016
/
Revised: 3 October 2016
/
Accepted: 9 November 2016
/
Published: 1 December 2016
Simple Summary
We show that whole-genome and transcriptome sequencing can be achieved within clinically effective timelines, yielding clinically useful and actionable information.
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. We show that whole-genome and transcriptome sequencing can be achieved within clinically effective timelines, yielding clinically useful and actionable information.
