Clinical implementation of genetic testing in adults for hereditary hematologic malignancy syndromes

Safa Ansar; Janet Malcolmson; Kirsten M Farncombe; Karen Yee; Raymond H Kim; Hassan Sibai

doi:10.1016/j.gim.2022.08.010

Clinical implementation of genetic testing in adults for hereditary hematologic malignancy syndromes

Genet Med. 2022 Nov;24(11):2367-2379. doi: 10.1016/j.gim.2022.08.010. Epub 2022 Sep 16.

Authors

Safa Ansar¹, Janet Malcolmson², Kirsten M Farncombe³, Karen Yee⁴, Raymond H Kim⁵, Hassan Sibai⁶

Affiliations

¹ Division of Medical Oncology and Hematology, Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada.
² Bhalwani Familial Cancer Clinic, Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada; Department of Molecular Genetics, University of Toronto, Toronto, Ontario, Canada.
³ Toronto General Hospital Research Institute, University Health Network, Toronto, Ontario, Canada.
⁴ Division of Medical Oncology and Hematology, Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada; Department of Medicine, University of Toronto, Toronto, Ontario, Canada.
⁵ Division of Medical Oncology and Hematology, Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada; Bhalwani Familial Cancer Clinic, Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada; Ontario Institute for Cancer Research, Toronto, Ontario, Canada; Division of Clinical and Metabolic Genetics, The Hospital for Sick Children, Toronto, Ontario, Canada; Sinai Health System, Toronto, Ontario, Canada; Department of Medicine, University of Toronto, Toronto, Ontario, Canada. Electronic address: Raymond.kim@uhn.ca.
⁶ Division of Medical Oncology and Hematology, Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada; Department of Medicine, University of Toronto, Toronto, Ontario, Canada. Electronic address: Hassan.Sibai@uhn.ca.

PMID: 36112138
DOI: 10.1016/j.gim.2022.08.010

Abstract

Purpose: As research on hereditary hematologic malignancy syndromes (HHMS) are accumulating, cancer genetics clinics are identifying more adult hematology patients with an inherited component to their disease. However, investigations for HHMS are complex, and there is no formal consensus on genetic testing criteria.

Methods: We developed genetic testing criteria for adult hematology patients through a comprehensive literature review and our experience at the Princess Margaret Cancer Centre. We validated our criteria by applying them retrospectively to patients referred to our clinic for HHMS assessment.

Results: Our genetic testing criteria are comprehensive of myeloid malignancies, lymphoid malignancies, and bone marrow failure, including age at diagnosis, family history, and genetic test results in blood and bone marrow. Of the 104 patients who met the criteria, 26% had at least 1 actionable variant in any gene associated with an increased risk of cancer and 13% had an actionable variant resulting in an HHMS diagnosis. A total of 15 patients had incidental findings, including 11 patients with a pathogenic variant associated with carrier status for an autosomal recessive disorder and 4 patients with a mosaic result.

Conclusion: Our high gene positivity rate shows the utility of a broad approach to germline testing in an adult hematology population.

Keywords: Genetic testing; Germline; Hematologic malignancy; Hereditary.

Publication types

Review
Research Support, Non-U.S. Gov't

MeSH terms

Adult
Bone Marrow
Genetic Predisposition to Disease
Genetic Testing*
Hematologic Neoplasms* / diagnosis
Hematologic Neoplasms* / epidemiology
Hematologic Neoplasms* / genetics
Humans
Medical History Taking
Retrospective Studies