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Cold Spring Harb Mol Case Stud. 2015 Oct;1(1):a000570. doi: 10.1101/mcs.a000570.

Lessons learned from the application of whole-genome analysis to the treatment of patients with advanced cancers.

Author information

1
British Columbia Cancer Agency, Division of Medical Oncology, Vancouver, British Columbia V5Z 4E6, Canada;
2
British Columbia Cancer Agency, Canada's Michael Smith Genome Sciences Centre, Vancouver, British Columbia V5Z 4E6, Canada;
3
British Columbia Cancer Agency Department of Molecular Oncology, BC Cancer Agency, Vancouver, British Columbia V5Z 1L3, Canada;
4
Department of Pediatrics, BC Children's Hospital, Vancouver, British Columbia V6H 3V4, Canada;
5
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;
6
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;
7
British Columbia Cancer Agency, Diagnostic Imaging Department, Vancouver, British Columbia V5Z 4E6, Canada;
8
Department of Medical Genetics, University of British Columbia, Vancouver, British Columbia V6T 1Z4, Canada.
9
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.

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.

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