Cascade testing for hereditary cancer: comprehensive multigene panels identify unexpected actionable findings in relatives

Brandie Heald*, Sara Pirzadeh-Miller, Rachel E. Ellsworth, Sarah M. Nielsen, Emily M. Russell, Peter Beitsch, Edward D. Esplin, Robert L. Nussbaum, Daniel E. Pineda-Alvarez, Allison W. Kurian, Heather Hampel

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

Current guidelines recommend single variant testing in relatives of patients with known pathogenic or likely pathogenic germline variants in cancer predisposition genes. This approach may preclude the use of risk-reducing strategies in family members who have pathogenic or likely pathogenic germline variants in other cancer predisposition genes. Cascade testing using multigene panels was performed in 3696 relatives of 7433 probands. Unexpected pathogenic or likely pathogenic germline variants were identified in 230 (6.2%) relatives, including 144 who were negative for the familial pathogenic or likely pathogenic variant but positive for a pathogenic or likely pathogenic variant in a different gene than the proband and 74 who tested positive for the familial pathogenic or likely pathogenic variant and had an additional pathogenic or likely pathogenic variant in a different gene than the proband. Of the relatives with unexpected pathogenic or likely pathogenic germline variants, 36.3% would have qualified for different or additional cancer screening recommendations. Limiting cascade testing to only the familial pathogenic or likely pathogenic variant would have resulted in missed, actionable findings for a subset of relatives.

Original languageEnglish
Pages (from-to)334-337
Number of pages4
JournalJournal of the National Cancer Institute
Volume116
Issue number2
DOIs
StatePublished - 1 Feb 2024
Externally publishedYes

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