title: Personalized oncogenomics in the management of gastrointestinal carcinomas-early experiences from a pilot study.
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 anIDH1somatic 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, aBRAFV600E mutation and wild-typeKRASprofile 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.
  
  
  CONCLUSIONS
  We show that whole-genome and transcriptome sequencing can be achieved within clinically effective timelines, yielding clinically useful and actionable information.
authors.affiliation: Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, BC.
authors.forename: B S
authors.initials: BS
authors.lastname: Sheffield
authors.affiliation: Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, BC.
authors.forename: B
authors.initials: B
authors.lastname: Tessier-Cloutier
authors.affiliation: Royal Victoria Regional Health Centre, Department of Pathology and Laboratory Medicine, Barrie, ON.
authors.forename: H
authors.initials: H
authors.lastname: Li-Chang
authors.affiliation: Canada's Michael Smith Genome Sciences Centre, BC Cancer Agency, Vancouver, BC.
authors.forename: Y
authors.initials: Y
authors.lastname: Shen
authors.affiliation: Canada's Michael Smith Genome Sciences Centre, BC Cancer Agency, Vancouver, BC.
authors.forename: E
authors.initials: E
authors.lastname: Pleasance
authors.affiliation: Canada's Michael Smith Genome Sciences Centre, BC Cancer Agency, Vancouver, BC.
authors.forename: K
authors.initials: K
authors.lastname: Kasaian
authors.affiliation: Canada's Michael Smith Genome Sciences Centre, BC Cancer Agency, Vancouver, BC.
authors.forename: Y
authors.initials: Y
authors.lastname: Li
authors.affiliation: Canada's Michael Smith Genome Sciences Centre, BC Cancer Agency, Vancouver, BC.
authors.forename: S J M
authors.initials: SJ
authors.lastname: Jones
authors.affiliation: Division of Medical Oncology, BC Cancer Agency, Vancouver, BC.
authors.forename: H J
authors.initials: HJ
authors.lastname: Lim
authors.affiliation: Division of Medical Oncology, BC Cancer Agency, Vancouver, BC.
authors.forename: D J
authors.initials: DJ
authors.lastname: Renouf
authors.affiliation: Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, BC.
authors.forename: D G
authors.initials: DG
authors.lastname: Huntsman
authors.affiliation: Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, BC.
authors.forename: S
authors.initials: S
authors.lastname: Yip
authors.affiliation: Division of Medical Oncology, BC Cancer Agency, Vancouver, BC.
authors.forename: J
authors.initials: J
authors.lastname: Laskin
authors.affiliation: Canada's Michael Smith Genome Sciences Centre, BC Cancer Agency, Vancouver, BC.; Department of Medical Genetics, University of British Columbia, Vancouver, BC.
authors.forename: M
authors.initials: M
authors.lastname: Marra
authors.affiliation: Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, BC.
authors.forename: D F
authors.initials: DF
authors.lastname: Schaeffer
keywords: Oncogenomics; appendiceal adenocarcinoma; bevacizumab; cholangiocarcinoma; colonic adenocarcinoma; genomics; personalized medicine; targeted therapy