Schuh, A;
Dreau, H;
Knight, SJL;
Ridout, K;
Mizani, T;
Vavoulis, D;
Colling, R;
... Taylor, JC; + view all
(2018)
Clinically actionable mutation profiles in patients with cancer identified by whole-genome sequencing.
Cold Spring Harbor Molecular Case Studies
, 4
(2)
, Article a002279. 10.1101/mcs.a002279.
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Abstract
Next-generation sequencing (NGS) efforts have established catalogs of mutations relevant to cancer development. However, the clinical utility of this information remains largely unexplored. Here, we present the results of the first eight patients recruited into a clinical whole-genome sequencing (WGS) program in the United Kingdom. We performed PCR-free WGS of fresh frozen tumors and germline DNA at 75× and 30×, respectively, using the HiSeq2500 HTv4. Subtracted tumor VCFs and paired germlines were subjected to comprehensive analysis of coding and noncoding regions, integration of germline with somatically acquired variants, and global mutation signatures and pathway analyses. Results were classified into tiers and presented to a multidisciplinary tumor board. WGS results helped to clarify an uncertain histopathological diagnosis in one case, led to informed or supported prognosis in two cases, leading to de-escalation of therapy in one, and indicated potential treatments in all eight. Overall 26 different tier 1 potentially clinically actionable findings were identified using WGS compared with six SNVs/indels using routine targeted NGS. These initial results demonstrate the potential of WGS to inform future diagnosis, prognosis, and treatment choice in cancer and justify the systematic evaluation of the clinical utility of WGS in larger cohorts of patients with cancer.
| Type: | Article |
|---|---|
| Title: | Clinically actionable mutation profiles in patients with cancer identified by whole-genome sequencing |
| Location: | United States |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1101/mcs.a002279 |
| Publisher version: | http://dx.doi.org/10.1101/mcs.a002279 |
| Language: | English |
| Additional information: | Copyright © 2018 Schuh et al.; Published by Cold Spring Harbor Laboratory Press. This article is distributed under the terms of the Creative Commons Attribution-Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/), which permits reuse and redistribution, except for commercial purposes, provided that the original author and source are credited. |
| Keywords: | colon cancer, cutaneous leiomyosarcoma, endometrial carcinoma, neoplasm of the breast, pharyngeal neoplasm, prostate cancer |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute > Research Department of Pathology |
| URI: | https://discovery-pp.ucl.ac.uk/id/eprint/10048374 |
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