title: Lessons learned from the application of whole-genome analysis to the treatment of patients with advanced cancers.
abstract: Given the success of targeted agents in specific populations it is expected that some degree of molecular biomarker testing will become standard of care for many, if not all, cancers. To facilitate this, cancer centers worldwide are experimenting with targeted "panel" sequencing of selected mutations. Recent advances in genomic technology enable the generation of genome-scale data sets for individual patients. Recognizing the risk, inherent in panel sequencing, of failing to detect meaningful somatic alterations, we sought to establish processes to integrate data from whole-genome analysis (WGA) into routine cancer care. Between June 2012 and August 2014, 100 adult patients with incurable cancers consented to participate in the Personalized OncoGenomics (POG) study. Fresh tumor and blood samples were obtained and used for whole-genome and RNA sequencing. Computational approaches were used to identify candidate driver mutations, genes, and pathways. Diagnostic and drug information were then sought based on these candidate "drivers." Reports were generated and discussed weekly in a multidisciplinary team setting. Other multidisciplinary working groups were assembled to establish guidelines on the interpretation, communication, and integration of individual genomic findings into patient care. Of 78 patients for whom WGA was possible, results were considered actionable in 55 cases. In 23 of these 55 cases, the patients received treatments motivated by WGA. Our experience indicates that a multidisciplinary team of clinicians and scientists can implement a paradigm in which WGA is integrated into the care of late stage cancer patients to inform systemic therapy decisions.
authors.affiliation: British Columbia Cancer Agency, Division of Medical Oncology, Vancouver, British Columbia V5Z 4E6, Canada;
authors.forename: Janessa
authors.initials: J
authors.lastname: Laskin
authors.affiliation: British Columbia Cancer Agency, Canada's Michael Smith Genome Sciences Centre, Vancouver, British Columbia V5Z 4E6, Canada;
authors.forename: Steven
authors.initials: S
authors.lastname: Jones
authors.affiliation: British Columbia Cancer Agency Department of Molecular Oncology, BC Cancer Agency, Vancouver, British Columbia V5Z 1L3, Canada;
authors.forename: Samuel
authors.initials: S
authors.lastname: Aparicio
authors.affiliation: British Columbia Cancer Agency, Division of Medical Oncology, Vancouver, British Columbia V5Z 4E6, Canada;
authors.forename: Stephen
authors.initials: S
authors.lastname: Chia
authors.affiliation: British Columbia Cancer Agency, Canada's Michael Smith Genome Sciences Centre, Vancouver, British Columbia V5Z 4E6, Canada;
authors.forename: Carolyn
authors.initials: C
authors.lastname: Ch'ng
authors.affiliation: Department of Pediatrics, BC Children's Hospital, Vancouver, British Columbia V6H 3V4, Canada;
authors.forename: Rebecca
authors.initials: R
authors.lastname: Deyell
authors.affiliation: British Columbia Cancer Agency Department of Molecular Oncology, BC Cancer Agency, Vancouver, British Columbia V5Z 1L3, Canada;
authors.forename: Peter
authors.initials: P
authors.lastname: Eirew
authors.affiliation: British Columbia Cancer Agency, Canada's Michael Smith Genome Sciences Centre, Vancouver, British Columbia V5Z 4E6, Canada;
authors.forename: Alexandra
authors.initials: A
authors.lastname: Fok
authors.affiliation: British Columbia Cancer Agency, Division of Medical Oncology, Vancouver, British Columbia V5Z 4E6, Canada;
authors.forename: Karen
authors.initials: K
authors.lastname: Gelmon
authors.affiliation: British Columbia Cancer Agency, Division of Medical Oncology, Vancouver, British Columbia V5Z 4E6, Canada;
authors.forename: Cheryl
authors.initials: C
authors.lastname: Ho
authors.affiliation: British Columbia Cancer Agency Department of Molecular Oncology, BC Cancer Agency, Vancouver, British Columbia V5Z 1L3, Canada;; University of British Columbia, Pathology and Laboratory Medicine, Vancouver, British Columbia V6T 1Z4, Canada;
authors.forename: David
authors.initials: D
authors.lastname: Huntsman
authors.affiliation: British Columbia Cancer Agency, Canada's Michael Smith Genome Sciences Centre, Vancouver, British Columbia V5Z 4E6, Canada;
authors.forename: Martin
authors.initials: M
authors.lastname: Jones
authors.affiliation: British Columbia Cancer Agency, Canada's Michael Smith Genome Sciences Centre, Vancouver, British Columbia V5Z 4E6, Canada;
authors.forename: Katayoon
authors.initials: K
authors.lastname: Kasaian
authors.affiliation: British Columbia Cancer Agency, Division of Medical Oncology, Vancouver, British Columbia V5Z 4E6, Canada;; British Columbia Cancer Agency, Canada's Michael Smith Genome Sciences Centre, Vancouver, British Columbia V5Z 4E6, Canada;
authors.forename: Aly
authors.initials: A
authors.lastname: Karsan
authors.affiliation: British Columbia Cancer Agency, Canada's Michael Smith Genome Sciences Centre, Vancouver, British Columbia V5Z 4E6, Canada;
authors.forename: Sreeja
authors.initials: S
authors.lastname: Leelakumari
authors.affiliation: British Columbia Cancer Agency, Canada's Michael Smith Genome Sciences Centre, Vancouver, British Columbia V5Z 4E6, Canada;
authors.forename: Yvonne
authors.initials: Y
authors.lastname: Li
authors.affiliation: British Columbia Cancer Agency, Division of Medical Oncology, Vancouver, British Columbia V5Z 4E6, Canada;
authors.forename: Howard
authors.initials: H
authors.lastname: Lim
authors.affiliation: British Columbia Cancer Agency, Canada's Michael Smith Genome Sciences Centre, Vancouver, British Columbia V5Z 4E6, Canada;
authors.forename: Yussanne
authors.initials: Y
authors.lastname: Ma
authors.affiliation: British Columbia Cancer Agency, Diagnostic Imaging Department, Vancouver, British Columbia V5Z 4E6, Canada;
authors.forename: Colin
authors.initials: C
authors.lastname: Mar
authors.affiliation: British Columbia Cancer Agency, Diagnostic Imaging Department, Vancouver, British Columbia V5Z 4E6, Canada;
authors.forename: Monty
authors.initials: M
authors.lastname: Martin
authors.affiliation: British Columbia Cancer Agency, Canada's Michael Smith Genome Sciences Centre, Vancouver, British Columbia V5Z 4E6, Canada;
authors.forename: Richard
authors.initials: R
authors.lastname: Moore
authors.affiliation: British Columbia Cancer Agency, Canada's Michael Smith Genome Sciences Centre, Vancouver, British Columbia V5Z 4E6, Canada;
authors.forename: Andrew
authors.initials: A
authors.lastname: Mungall
authors.affiliation: British Columbia Cancer Agency, Canada's Michael Smith Genome Sciences Centre, Vancouver, British Columbia V5Z 4E6, Canada;
authors.forename: Karen
authors.initials: K
authors.lastname: Mungall
authors.affiliation: British Columbia Cancer Agency, Canada's Michael Smith Genome Sciences Centre, Vancouver, British Columbia V5Z 4E6, Canada;
authors.forename: Erin
authors.initials: E
authors.lastname: Pleasance
authors.affiliation: Department of Pediatrics, BC Children's Hospital, Vancouver, British Columbia V6H 3V4, Canada;
authors.forename: S Rod
authors.initials: SR
authors.lastname: Rassekh
authors.affiliation: British Columbia Cancer Agency, Division of Medical Oncology, Vancouver, British Columbia V5Z 4E6, Canada;
authors.forename: Daniel
authors.initials: D
authors.lastname: Renouf
authors.affiliation: British Columbia Cancer Agency, Canada's Michael Smith Genome Sciences Centre, Vancouver, British Columbia V5Z 4E6, Canada;
authors.forename: Yaoqing
authors.initials: Y
authors.lastname: Shen
authors.affiliation: British Columbia Cancer Agency, Canada's Michael Smith Genome Sciences Centre, Vancouver, British Columbia V5Z 4E6, Canada;
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Schein
authors.affiliation: Department of Medical Genetics, University of British Columbia, Vancouver, British Columbia V6T 1Z4, Canada.
authors.forename: Kasmintan
authors.initials: K
authors.lastname: Schrader
authors.affiliation: British Columbia Cancer Agency, Division of Medical Oncology, Vancouver, British Columbia V5Z 4E6, Canada;
authors.forename: Sophie
authors.initials: S
authors.lastname: Sun
authors.affiliation: British Columbia Cancer Agency, Division of Medical Oncology, Vancouver, British Columbia V5Z 4E6, Canada;
authors.forename: Anna
authors.initials: A
authors.lastname: Tinker
authors.affiliation: British Columbia Cancer Agency, Canada's Michael Smith Genome Sciences Centre, Vancouver, British Columbia V5Z 4E6, Canada;
authors.forename: Eric
authors.initials: E
authors.lastname: Zhao
authors.affiliation: British Columbia Cancer Agency, Division of Medical Oncology, Vancouver, British Columbia V5Z 4E6, Canada;
authors.forename: Stephen
authors.initials: S
authors.lastname: Yip
authors.affiliation: British Columbia Cancer Agency, Canada's Michael Smith Genome Sciences Centre, Vancouver, British Columbia V5Z 4E6, Canada;; Department of Medical Genetics, University of British Columbia, Vancouver, British Columbia V6T 1Z4, Canada.
authors.forename: Marco A
authors.initials: MA
authors.lastname: Marra