. 2021 Mar;147(3):871-879.

doi: 10.1007/s00432-020-03377-6. Epub 2020 Sep 3.

Multigene panel testing for hereditary breast and ovarian cancer in the province of Ontario

Jordan Lerner-Ellis^{1

2

3}, Chloe Mighton^#^{4

5

6}, Conxi Lazaro^#^{4

7

8}, Nicholas Watkins^{4

9}, Vanessa Di Gioacchino⁴, Andrew Wong⁴, Martin C Chang^{10

11}, George S Charames^{10

4

12}

Affiliations

¹ Department of Laboratory Medicine and Pathobiology, University of Toronto, 600 University Avenue, Toronto, ON, M5G 1X5, Canada. Jordan.Lerner-Ellis@SinaiHealth.ca.
² Department of Pathology and Laboratory Medicine, Mount Sinai Hospital, Sinai Health, Toronto, ON, Canada. Jordan.Lerner-Ellis@SinaiHealth.ca.
³ Lunenfeld-Tanenbaum Research Institute, Sinai Health, Toronto, ON, Canada. Jordan.Lerner-Ellis@SinaiHealth.ca.
⁴ Department of Pathology and Laboratory Medicine, Mount Sinai Hospital, Sinai Health, Toronto, ON, Canada.
⁵ Institute of Health Policy, Management and Evaluation, University of Toronto, Toronto, ON, Canada.
⁶ Genomics Health Services Research Program, Li Ka Shing Knowledge Institute, St. Michael's Hospital, Toronto, ON, Canada.
⁷ Hereditary Cancer Program, ICO-IDIBELL, Barcelona, Spain.
⁸ Women's College Research Institute, Women's College Hospital, Toronto, ON, Canada.
⁹ Department of Molecular Genetics, University of Toronto, Toronto, ON, Canada.
¹⁰ Department of Laboratory Medicine and Pathobiology, University of Toronto, 600 University Avenue, Toronto, ON, M5G 1X5, Canada.
¹¹ University of Vermont Cancer Center, Burlington, VT, USA.
¹² Lunenfeld-Tanenbaum Research Institute, Sinai Health, Toronto, ON, Canada.

^# Contributed equally.

PMID: 32885271
PMCID: PMC11802097
DOI: 10.1007/s00432-020-03377-6

Multigene panel testing for hereditary breast and ovarian cancer in the province of Ontario

Jordan Lerner-Ellis et al. J Cancer Res Clin Oncol. 2021 Mar.

. 2021 Mar;147(3):871-879.

doi: 10.1007/s00432-020-03377-6. Epub 2020 Sep 3.

Authors

Affiliations

¹ Department of Laboratory Medicine and Pathobiology, University of Toronto, 600 University Avenue, Toronto, ON, M5G 1X5, Canada. Jordan.Lerner-Ellis@SinaiHealth.ca.
² Department of Pathology and Laboratory Medicine, Mount Sinai Hospital, Sinai Health, Toronto, ON, Canada. Jordan.Lerner-Ellis@SinaiHealth.ca.
³ Lunenfeld-Tanenbaum Research Institute, Sinai Health, Toronto, ON, Canada. Jordan.Lerner-Ellis@SinaiHealth.ca.
⁴ Department of Pathology and Laboratory Medicine, Mount Sinai Hospital, Sinai Health, Toronto, ON, Canada.
⁵ Institute of Health Policy, Management and Evaluation, University of Toronto, Toronto, ON, Canada.
⁶ Genomics Health Services Research Program, Li Ka Shing Knowledge Institute, St. Michael's Hospital, Toronto, ON, Canada.
⁷ Hereditary Cancer Program, ICO-IDIBELL, Barcelona, Spain.
⁸ Women's College Research Institute, Women's College Hospital, Toronto, ON, Canada.
⁹ Department of Molecular Genetics, University of Toronto, Toronto, ON, Canada.
¹⁰ Department of Laboratory Medicine and Pathobiology, University of Toronto, 600 University Avenue, Toronto, ON, M5G 1X5, Canada.
¹¹ University of Vermont Cancer Center, Burlington, VT, USA.
¹² Lunenfeld-Tanenbaum Research Institute, Sinai Health, Toronto, ON, Canada.

^# Contributed equally.

PMID: 32885271
PMCID: PMC11802097
DOI: 10.1007/s00432-020-03377-6

Erratum in

Correction to: Multigene panel testing for hereditary breast and ovarian cancer in the province of Ontario.
Lerner-Ellis J, Mighton C, Lazaro C, Watkins N, Di Gioacchino V, Wong A, Chang MC, Charames GS. Lerner-Ellis J, et al. J Cancer Res Clin Oncol. 2021 Aug;147(8):2487. doi: 10.1007/s00432-020-03399-0. J Cancer Res Clin Oncol. 2021. PMID: 32975687 Free PMC article. No abstract available.

Abstract

Purpose: 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).

Methods: 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.

Results: 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).

Conclusions: 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.

Keywords: Breast cancer; Genetic testing; Multigene panel testing; Next-generation sequencing; Ovarian cancer.

PubMed Disclaimer

Conflict of interest statement

The authors declare no competing interests.

Figures

**Fig. 1**
Proportion of pathogenic/likely pathogenic variants reported in positive cases in each gene. Total number of pathogenic (P) and likely pathogenic (LP) variants reported (n = 300) is greater than the total number of positive cases (n = 295), because five cases received two different P/LP variants. Heterozygous P/LP *MUTYH* variants are not included in these counts as those were considered an inconclusive result, not positive

**Fig. 2**
Ratio of inconclusive to positive results by gene. A ratio of more than one indicates that there were more inconclusive than positive results identified

See this image and copyright information in PMC

References

1. Burke W, Laberge AM, Press N (2010) Debating clinical utility. Public Health Genomics 13(4):215–223. 10.1159/000279623 - PMC - PubMed
1. Buys SS, Sandbach JF, Gammon A, Patel G, Kidd J, Brown KL et al (2017) A study of over 35,000 women with breast cancer tested with a 25-gene panel of hereditary cancer genes. Cancer 123(10):1721–1730. 10.1002/cncr.30498 - PubMed
1. Cybulski C, Wokolorczyk D, Jakubowska A, Huzarski T, Byrski T, Gronwald J et al (2011) Risk of breast cancer in women with a CHEK2 mutation with and without a family history of breast cancer. J Clin Oncol 29(28):3747–3752. 10.1200/jco.2010.34.0778 - PubMed
1. Dossa F, Cusimano MC, Sutradhar R, Metcalfe K, Little T, Lerner-Ellis J et al (2018) Real-world health services utilisation and outcomes after BRCA1 and BRCA2 testing in Ontario, Canada: the What Comes Next Cohort Study protocol. BMJ Open 8(9):e025317. 10.1136/bmjopen-2018-025317 - PMC - PubMed
1. Feliubadalo L, Lopez-Fernandez A, Pineda M, Diez O, Del Valle J, Gutierrez-Enriquez S et al (2019) Opportunistic testing of BRCA1, BRCA2 and mismatch repair genes improves the yield of phenotype driven hereditary cancer gene panels. Int J Cancer 145(10):2682–2691. 10.1002/ijc.32304 - PubMed

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Multigene panel testing for hereditary breast and ovarian cancer in the province of Ontario

Affiliations

Multigene panel testing for hereditary breast and ovarian cancer in the province of Ontario

Authors

Affiliations

Erratum in

Abstract

Conflict of interest statement

Figures

References

MeSH terms

Supplementary concepts

LinkOut - more resources

Full Text Sources

Medical

Miscellaneous