Implementation of Whole-Genome and Transcriptome Sequencing Into Clinical Cancer Care

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PURPOSE

The combination of whole-genome and transcriptome sequencing (WGTS) is expected to transform diagnosis and treatment for patients with cancer. WGTS is a comprehensive precision diagnostic test that is starting to replace the standard of care for oncology molecular testing in health care systems around the world; however, the implementation and widescale adoption of this best-in-class testing is lacking.

METHODS

Here, we address the barriers in integrating WGTS for cancer diagnostics and treatment selection and answer questions regarding utility in different cancer types, cost-effectiveness and affordability, and other practical considerations for WGTS implementation.

RESULTS

We review the current studies implementing WGTS in health care systems and provide a synopsis of the clinical evidence and insights into practical considerations for WGTS implementation. We reflect on regulatory, costs, reimbursement, and incidental findings aspects of this test.

CONCLUSION

WGTS is an appropriate comprehensive clinical test for many tumor types and can replace multiple, cascade testing approaches currently performed. Decreasing sequencing cost, increasing number of clinically relevant aberrations and discovery of more complex biomarkers of treatment response, should pave the way for health care systems and laboratories in implementing WGTS into clinical practice, to transform diagnosis and treatment for patients with cancer.

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Most cited references 72

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Cancer statistics, 2019

Rebecca Siegel, Kimberly D Miller, Ahmedin Jemal (2019)

Each year, the American Cancer Society estimates the numbers of new cancer cases and deaths that will occur in the United States and compiles the most recent data on cancer incidence, mortality, and survival. Incidence data, available through 2015, were collected by the Surveillance, Epidemiology, and End Results Program; the National Program of Cancer Registries; and the North American Association of Central Cancer Registries. Mortality data, available through 2016, were collected by the National Center for Health Statistics. In 2019, 1,762,450 new cancer cases and 606,880 cancer deaths are projected to occur in the United States. Over the past decade of data, the cancer incidence rate (2006-2015) was stable in women and declined by approximately 2% per year in men, whereas the cancer death rate (2007-2016) declined annually by 1.4% and 1.8%, respectively. The overall cancer death rate dropped continuously from 1991 to 2016 by a total of 27%, translating into approximately 2,629,200 fewer cancer deaths than would have been expected if death rates had remained at their peak. Although the racial gap in cancer mortality is slowly narrowing, socioeconomic inequalities are widening, with the most notable gaps for the most preventable cancers. For example, compared with the most affluent counties, mortality rates in the poorest counties were 2-fold higher for cervical cancer and 40% higher for male lung and liver cancers during 2012-2016. Some states are home to both the wealthiest and the poorest counties, suggesting the opportunity for more equitable dissemination of effective cancer prevention, early detection, and treatment strategies. A broader application of existing cancer control knowledge with an emphasis on disadvantaged groups would undoubtedly accelerate progress against cancer.

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The repertoire of mutational signatures in human cancer

Ludmil Alexandrov, Jaegil Kim, Nicholas J Haradhvala … (2020)

Somatic mutations in cancer genomes are caused by multiple mutational processes, each of which generates a characteristic mutational signature 1 . Here, as part of the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium 2 of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA), we characterized mutational signatures using 84,729,690 somatic mutations from 4,645 whole-genome and 19,184 exome sequences that encompass most types of cancer. We identified 49 single-base-substitution, 11 doublet-base-substitution, 4 clustered-base-substitution and 17 small insertion-and-deletion signatures. The substantial size of our dataset, compared with previous analyses 3–15 , enabled the discovery of new signatures, the separation of overlapping signatures and the decomposition of signatures into components that may represent associated—but distinct—DNA damage, repair and/or replication mechanisms. By estimating the contribution of each signature to the mutational catalogues of individual cancer genomes, we revealed associations of signatures to exogenous or endogenous exposures, as well as to defective DNA-maintenance processes. However, many signatures are of unknown cause. This analysis provides a systematic perspective on the repertoire of mutational processes that contribute to the development of human cancer.

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The 5th edition of the World Health Organization Classification of Haematolymphoid Tumours: Myeloid and Histiocytic/Dendritic Neoplasms

Joseph D. Khoury, Eric Solary, Oussama Abla … (2022)

The upcoming 5th edition of the World Health Organization (WHO) Classification of Haematolymphoid Tumours is part of an effort to hierarchically catalogue human cancers arising in various organ systems within a single relational database. This paper summarizes the new WHO classification scheme for myeloid and histiocytic/dendritic neoplasms and provides an overview of the principles and rationale underpinning changes from the prior edition. The definition and diagnosis of disease types continues to be based on multiple clinicopathologic parameters, but with refinement of diagnostic criteria and emphasis on therapeutically and/or prognostically actionable biomarkers. While a genetic basis for defining diseases is sought where possible, the classification strives to keep practical worldwide applicability in perspective. The result is an enhanced, contemporary, evidence-based classification of myeloid and histiocytic/dendritic neoplasms, rooted in molecular biology and an organizational structure that permits future scalability as new discoveries continue to inexorably inform future editions.

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Author and article information

Journal

Journal ID (nlm-ta): JCO Precis Oncol

Journal ID (iso-abbrev): JCO Precis Oncol

Journal ID (hwp): po

Journal ID (publisher-id): PO

Title: JCO Precision Oncology

Publisher: Wolters Kluwer Health

ISSN (Electronic): 2473-4284

Publication date Collection: 2022

Publication date (Electronic): 8 December 2022

Publication date PMC-release: 8 December 2022

Volume: 6

Electronic Location Identifier: e2200245

Affiliations

[ ¹ ]Hartwig Medical Foundation, Amsterdam, the Netherlands

[ ² ]Center for Molecular Medicine and Oncode Institute, University Medical Center, Utrecht, the Netherlands

[ ³ ]Caryl and Israel Englander Institute for Precision Medicine, Weill Cornell Medicine, New York, NY

[ ⁴ ]Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden

[ ⁵ ]Clinical Genetics, Karolinska University Hospital, Solna, Sweden

[ ⁶ ]Illumina Productos de España, S.L.U., Plaza Pablo Ruiz Picasso, Madrid, Spain

[ ⁷ ]Erasmus School of Health Policy & Management, Erasmus University, Rotterdam, the Netherlands

[ ⁸ ]Centre for Cancer Research, University of Melbourne, Melbourne, Australia

[ ⁹ ]Université de Paris, CRESS, INSERM, INRA, URCEco, AP-HP, Hôpital de l'Hôtel Dieu, Paris, France

[ ¹⁰ ]Julius Center for Health Sciences and Primary Care, University Medical Center, Utrecht, the Netherlands

[ ¹¹ ]Department of Health, Medicine and Caring Sciences (HMV), Linköping University, Linköping, Sweden

[ ¹² ]Department of Pathology, St Jude Children's Research Hospital, Memphis, TN

[ ¹³ ]Institute of Pathology, University Hospital Cologne, Germany

[ ¹⁴ ]Department of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada

[ ¹⁵ ]Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada

[ ¹⁶ ]Ontario Institute for Cancer Research, Toronto, Ontario, Canada

[ ¹⁷ ]Cancer Research UK Cambridge Institute and Department of Oncology, University of Cambridge, Cambridge, United Kingdom

[ ¹⁸ ]Institut Gustave Roussy, Villejuif, France

[ ¹⁹ ]Stichting Lygature, Utrecht, the Netherlands

[ ²⁰ ]Institut d’Investigacions Biomèdiques August Pi I Sunyer (IDIBAPS), Barcelona, Spain

[ ²¹ ]Centro de Investigación Biomédica en Red, Cáncer (CIBERONC), Madrid, Spain

[ ²² ]Hematopathology Unit, Hospital Clínic of Barcelona, Barcelona, Spain

[ ²³ ]University of Barcelona, Barcelona, Spain

[ ²⁴ ]University of Oxford, Oxford, United Kingdom

[ ²⁵ ]Laboratory for Cancer Genomics, RIKEN Center for Integrative Medical Sciences, Kanagawa, Japan

[ ²⁶ ]Berlin Institute of Health at Charité—Universitätsmedizin Berlin, Clinical Study Center, Berlin, Germany

[ ²⁷ ]Munich Leukemia Laboratory, Munich, Germany

[ ²⁸ ]Division of Translational Medical Oncology, German Cancer Research Center (DKFZ) and National Center for Tumor Diseases (NCT), Heidelberg, Germany

[ ²⁹ ]German Cancer Consortium (DKTK), Heidelberg, Germany

[ ³⁰ ]New York Genome Center; Department of Pathology, Columbia University Irving Medical Center, New York, NY