Feasibility of whole-genome sequencing-based tumor diagnostics in routine pathology practice
Samsom, Kris G; Schipper, Luuk J; Roepman, Paul; Bosch, Linda Jw; Lalezari, Ferry; Klompenhouwer, Elisabeth G; de Langen, Adrianus J; Buffart, Tineke E; Riethorst, Immy; Schoenmaker, Lieke; Schout, Daoin; van der Noort, Vincent; van den Berg, Jose G; de Bruijn, Ewart; van der Hoeven, Jacobus Jm; van Snellenberg, Hans; van der Kolk, Lizet E; Cuppen, Edwin; Voest, Emile E; Meijer, Gerrit A; Monkhorst, Kim
(2022) Journal of Pathology, volume 258, issue 2, pp. 179 - 188
(Article)
Abstract
The current increase in number and diversity of targeted anticancer agents poses challenges to the logistics and timeliness of molecular diagnostics (MolDx), resulting in underdiagnosis and treatment. Whole-genome sequencing (WGS) may provide a sustainable solution for addressing current as well as future diagnostic challenges. The present study therefore aimed to
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prospectively assess feasibility, validity, and value of WGS in routine clinical practice. WGS was conducted independently of, and in parallel with, standard of care (SOC) diagnostics on routinely obtained tumor samples from 1,200 consecutive patients with metastatic cancer. Results from both tests were compared and discussed in a dedicated tumor board. From 1,200 patients, 1,302 samples were obtained, of which 1,216 contained tumor cells. WGS was successful in 70% (854/1,216) of samples with a median turnaround time of 11 days. Low tumor purity (<20%) was the main reason for not completing WGS. WGS identified 99.2% and SOC MolDx 99.7% of the total of 896 biomarkers found in genomic regions covered by both tests. Actionable biomarkers were found in 603/848 patients (71%). Of the 936 associated therapy options identified by WGS, 343 were identified with SOC MolDx (36.6%). Biomarker-based therapy was started in 147 patients. WGS revealed 49 not previously identified pathogenic germline variants. Fresh-frozen, instead of formalin-fixed and paraffin-embedded, sample logistics were easily adopted as experienced by the professionals involved. WGS for patients with metastatic cancer is well feasible in routine clinical practice, successfully yielding comprehensive genomic profiling for the vast majority of patients. © 2022 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.
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Keywords: cancer, diagnostics, DNA sequencing, precision oncology, whole genome sequencing Biomarker, Pathology and Forensic Medicine, Journal Article
ISSN: 0022-3417
Publisher: John Wiley and Sons Ltd
Note: Funding Information: The authors thank the following members of the Pathology Department of the Netherlands Cancer Institute: Petur Snaebjornsson, Liudmila Kodach, Maurits van Montfoort, Claudie Flohil, Elise Bekers, Laura Smit, Hester van Boven, Hugo Horlings, Bart van de Wiel, Joyce Sanders, Emilie Groen, Mijke Bol, Jacqueline van der Wal, Mathilde Almekinders, Efraim Rosenberg, Mirjam Boelens, Frans Hogervorst, Jelle Wesseling, Lisette Forrer, Annegien Broeks, Petra Nederlof, and Tom van Wezel for implementing the WGS workflow and the interpretation of sequencing data. Furthermore, we thank the laboratory technicians: Jan-Nico Ridderbos, Kelly van Deventer, Saphira van Diest, Angelique van Dam, Sandra van der Slikke-Meijvogel, Nicoline Woudsma, Tim Niessen, Candy van Riel, Jaschenka Houtgraaf, Irene Hegger, Selena Jevtic, Assia Bourdoudi, Unga Unmehopa, Mickey Dukic, Isis van Hallem, Maarten Breet, and Verena Koning for adopting and executing the fresh-frozen workflow and organizing all the involved logistics. Likewise, we thank the following clinicians and research nurses: Willemijn Theelen, Marieke Vollebergh, Egbert Smit, Wanda de Kanter, Winette van der Graaf, Marloes van Dongen, Martin Rijlaarsdam, Wieneke Buikhuisen, Sandra Visser, and Judith Westra for their active role in the recruitment of patients. We thank Tarik Baetens for his role in tissue retrieval and Simone Koole, Geert Frederix, and Valesca Retèl for Health Technology Assessment advice. We thank ZonMw (the Netherlands Organization for Health Research and Development) and the Hartwig Medical Foundation for funding the study. The WIDE is funded by ZonMw, the Netherlands Organization for Health Research and Development (Project No. 446002004), including an in-kind contribution of the Hartwig Medical Foundation. The study protocol has been independently peer-reviewed by ZonMw. ZonMw had no role in the design nor the collection, analysis, and interpretation of the data, nor the writing of the article. Health-RI is acknowledged for providing research infrastructure support. Funding Information: The authors thank the following members of the Pathology Department of the Netherlands Cancer Institute: Petur Snaebjornsson, Liudmila Kodach, Maurits van Montfoort, Claudie Flohil, Elise Bekers, Laura Smit, Hester van Boven, Hugo Horlings, Bart van de Wiel, Joyce Sanders, Emilie Groen, Mijke Bol, Jacqueline van der Wal, Mathilde Almekinders, Efraim Rosenberg, Mirjam Boelens, Frans Hogervorst, Jelle Wesseling, Lisette Forrer, Annegien Broeks, Petra Nederlof, and Tom van Wezel for implementing the WGS workflow and the interpretation of sequencing data. Furthermore, we thank the laboratory technicians: Jan‐Nico Ridderbos, Kelly van Deventer, Saphira van Diest, Angelique van Dam, Sandra van der Slikke‐Meijvogel, Nicoline Woudsma, Tim Niessen, Candy van Riel, Jaschenka Houtgraaf, Irene Hegger, Selena Jevtic, Assia Bourdoudi, Unga Unmehopa, Mickey Dukic, Isis van Hallem, Maarten Breet, and Verena Koning for adopting and executing the fresh‐frozen workflow and organizing all the involved logistics. Likewise, we thank the following clinicians and research nurses: Willemijn Theelen, Marieke Vollebergh, Egbert Smit, Wanda de Kanter, Winette van der Graaf, Marloes van Dongen, Martin Rijlaarsdam, Wieneke Buikhuisen, Sandra Visser, and Judith Westra for their active role in the recruitment of patients. We thank Tarik Baetens for his role in tissue retrieval and Simone Koole, Geert Frederix, and Valesca Retèl for Health Technology Assessment advice. We thank ZonMw (the Netherlands Organization for Health Research and Development) and the Hartwig Medical Foundation for funding the study. The WIDE is funded by ZonMw, the Netherlands Organization for Health Research and Development (Project No. 446002004), including an in‐kind contribution of the Hartwig Medical Foundation. The study protocol has been independently peer‐reviewed by ZonMw. ZonMw had no role in the design nor the collection, analysis, and interpretation of the data, nor the writing of the article. Health‐RI is acknowledged for providing research infrastructure support. Publisher Copyright: © 2022 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.
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