Analytical demands to use whole-genome sequencing in precision oncology
Meggendorfer, Manja; Jobanputra, Vaidehi; Wrzeszczynski, Kazimierz O.; Roepman, Paul; de Bruijn, Ewart; Cuppen, Edwin; Buttner, Reinhard; Caldas, Carlos; Grimmond, Sean; Mullighan, Charles G.; Elemento, Olivier; Rosenquist, Richard; Schuh, Anna; Haferlach, Torsten
(2022) Seminars in Cancer Biology, volume 84, pp. 16 - 22
(Article)
Abstract
Interrogating the tumor genome in its entirety by whole-genome sequencing (WGS) offers an unprecedented insight into the biology and pathogenesis of cancer, with potential impact on diagnostics, prognostication and therapy selection. WGS is able to detect sequence as well as structural variants and thereby combines central domains of cytogenetics and
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molecular genetics. Given the potential of WGS in directing targeted therapeutics and clinical decision-making, we envision a gradual transition of the method from research to clinical routine. This review is one out of three within this issue aimed at facilitating this effort, by discussing in-depth analytical validation, clinical interpretation and clinical utility of WGS. The review highlights the requirements for implementing, validating and maintaining a clinical WGS pipeline to obtain high-quality patient-specific data in accordance with the local regulatory landscape. Every step of the WGS pipeline, which includes DNA extraction, library preparation, sequencing, bioinformatics analysis, and data storage, is considered with respect to its logistics, necessities, potential pitfalls, and the required quality management. WGS is likely to drive clinical diagnostics and patient care forward, if requirements and challenges of the technique are recognized and met.
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Keywords: Analytical validation, Clinical WGS, Precision oncology, WGS in routine diagnostics, Whole-genome sequencing, Cancer Research
ISSN: 1044-579X
Publisher: Academic Press Inc.
Note: Funding Information: The research was funded/supported by the National Institute for Health Research (NIHR)Oxford Biomedical Research Centre (BRC). The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR or the Department of Health. RR received funding from the Swedish Cancer Society, the Swedish Research Council, the Knut and Alice Wallenberg Foundation, Karolinska Institutet, Karolinska University Hospital, and Radiumhemmets Forsknings fonder. Funding Information: The research was funded/supported by the National Institute for Health Research (NIHR) Oxford Biomedical Research Centre (BRC) . The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR or the Department of Health. RR received funding from the Swedish Cancer Society , the Swedish Research Council , the Knut and Alice Wallenberg Foundation , Karolinska Institutet , Karolinska University Hospital , and Radiumhemmets Forsknings fonder . Publisher Copyright: © 2021 The Authors
(Peer reviewed)