Diagnostic yield of multigene panel testing in an Israeli cohort: enrichment of low-penetrance variants.
Breast Cancer Res Treat
; 181(2): 445-453, 2020 Jun.
Article
in En
| MEDLINE
| ID: mdl-32303989
ABSTRACT
BACKGROUND:
Carriers of pathogenic variants (PVs) in moderate-high-penetrance cancer susceptibility genes are offered tailored surveillance schemes for early cancer diagnosis. The clinical implications of low-penetrance variant carriers are less clear.METHODS:
Clinical and demographic data were retrieved for a cohort of Israeli individuals who underwent oncogenetic testing by the 30-gene cancer panel at Color Genomics laboratory, between 04/2013 and 12/2018.RESULTS:
Of 758 genotyped individuals, 504 had been diagnosed with cancer prior to testing 283 (56%) had breast cancer and 106 (21%) colorectal cancer. Pathogenic or likely pathogenic (P/LP) variants were detected in 123 (16%) individuals. Overall, 44 different P/LP variants were detected in 18/30 cancer susceptibility genes; 20 of them were founder/recurrent mutations. Of the carriers, 39 (32%), 10 (8%), and 74 (60%) carried high-, moderate-, or low-penetrance variants, respectively. After excluding low-penetrance variants, 7% (33/504) of all cancer patients, 6% of breast or ovarian cancer patients were found to be carriers, as well as 7% (14/203) of individuals with colonic polyps, and 4% (11/254) of cancer-free individuals.CONCLUSIONS:
The diagnostic yield of moderate- and high-penetrance PVs using multigene panel testing was 6%, with 3.7% carriers of non-recurrent PVs. This yield should be discussed during pre-test counseling, and emphasizes the need for harmonized recommendations regarding clinical implications of low-penetrance variants.Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Breast Neoplasms
/
Ethnicity
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Biomarkers, Tumor
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Genetic Testing
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Genetic Predisposition to Disease
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Early Detection of Cancer
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Mutation
Type of study:
Diagnostic_studies
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Etiology_studies
/
Guideline
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Incidence_studies
/
Observational_studies
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Prognostic_studies
/
Risk_factors_studies
/
Screening_studies
Limits:
Adolescent
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Adult
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Aged
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Aged80
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Female
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Humans
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Middle aged
Country/Region as subject:
Asia
Language:
En
Journal:
Breast Cancer Res Treat
Year:
2020
Type:
Article
Affiliation country:
Israel