The aim of this study was to determine the diagnostic yield of multigene panel testing among patients referred with hereditary breast and ovarian cancer (HBOC).
Patients who met provincial eligibility criteria were tested at the Advanced Molecular Diagnostic Laboratory at Mount Sinai Hospital, Toronto. Gene sequencing and exon-level copy number variant (CNV) analysis was performed. The referring physician had the opportunity to choose between several different gene panels based on patient phenotype. Cases were included in the analysis based on personal and family history of cancer and the type of panel ordered.
3251 cases that received panel testing were included in this analysis. Overall, 9.1% (295) had a positive (pathogenic or likely pathogenic) result and 27.1% (882) had an inconclusive result (variant of uncertain significance). The genes with the highest prevalence of positive results were in BRCA2 (2.2%, 71/3235), BRCA1 (1.9%, 62/3235), and CHEK2 (1.4%, 40/2916). Of the positive cases, 9.8% (29) had a pathogenic or likely pathogenic variant in a gene associated with Lynch syndrome (MSH6, MSH2, MLH1, or PMS2).
Our overall positive yield is similar to that reported in the literature. The yield of inconclusive results was three times that of positive results. By testing more individuals in families with HBOC and through data-sharing efforts, the clinical significance of most variants may eventually be determined and panel testing for monogenic cancer predisposition syndromes will have greater utility.
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This study was supported by the Ontario Ministry of Health. C.M. receives support from the Canadian Institutes of Health Research (GSD-164222). C.L. was a visiting scientist at Pathology and Laboratory Medicine, Mount Sinai Hospital and Women’s College Hospital thanks to Salvador Madariaga (PRX18/00267) and M-BAE (BA18/00018) grants (Spanish Government). We thank all of the clinicians who submitted the samples to our laboratory for testing. We would like to thank the laboratory staff who performed the work: E. Agro, A. Belay, E. Cox, S. Crafter, N. Di Nicola, K. Fenwick, K. Hamilton, A. Kiselova, G. Lee-Inniss, A. Lima Garay, J. Marr, J. Mayers, S. McArthur, A. Mitri, N. Moujani, O. Zeynep, S. Tancredi, K. Wagner, D. Yee, K.R. Zakoor, and M. Zhivotyagina.
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Ethical approval was obtained from the Research Ethics Board (REB) of Mount Sinai Hospital.
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Lerner-Ellis, J., Mighton, C., Lazaro, C. et al. Multigene panel testing for hereditary breast and ovarian cancer in the province of Ontario. J Cancer Res Clin Oncol 147, 871–879 (2021). https://doi.org/10.1007/s00432-020-03377-6
- Multigene panel testing
- Breast cancer
- Ovarian cancer
- Genetic testing
- Next-generation sequencing