Lessons learned from the application of whole-genome analysis to the treatment of patients with advanced cancers
- Janessa Laskin1,
- Steven Jones2,
- Samuel Aparicio3,
- Stephen Chia1,
- Carolyn Ch'ng2,
- Rebecca Deyell4,
- Peter Eirew3,
- Alexandra Fok2,
- Karen Gelmon1,
- Cheryl Ho1,
- David Huntsman3,5,
- Martin Jones2,
- Katayoon Kasaian2,
- Aly Karsan1,2,
- Sreeja Leelakumari2,
- Yvonne Li2,
- Howard Lim1,
- Yussanne Ma2,
- Colin Mar6,
- Monty Martin6,
- Richard Moore2,
- Andrew Mungall2,
- Karen Mungall2,
- Erin Pleasance2,
- S. Rod Rassekh4,
- Daniel Renouf1,
- Yaoqing Shen2,
- Jacqueline Schein2,
- Kasmintan Schrader7,
- Sophie Sun1,
- Anna Tinker1,
- Eric Zhao2,
- Stephen Yip1 and
- Marco A. Marra2,7
- 1British Columbia Cancer Agency, Division of Medical Oncology, Vancouver, British Columbia V5Z 4E6, Canada;
- 2British Columbia Cancer Agency, Canada's Michael Smith Genome Sciences Centre, Vancouver, British Columbia V5Z 4E6, Canada;
- 3British Columbia Cancer Agency Department of Molecular Oncology, BC Cancer Agency, Vancouver, British Columbia V5Z 1L3, Canada;
- 4Department of Pediatrics, BC Children's Hospital, Vancouver, British Columbia V6H 3V4, Canada;
- 5University of British Columbia, Pathology and Laboratory Medicine, Vancouver, British Columbia V6T 1Z4, Canada;
- 6British Columbia Cancer Agency, Diagnostic Imaging Department, Vancouver, British Columbia V5Z 4E6, Canada;
- 7Department of Medical Genetics, University of British Columbia, Vancouver, British Columbia V6T 1Z4, Canada
- Corresponding author: jlaskin{at}bccancer.bc.ca
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.
- Received July 21, 2015.
- Accepted August 7, 2015.
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