Cascade testing for hereditary cancer: comprehensive multigene panels identify unexpected actionable findings in relatives. Journal of the National Cancer Institute Heald, B., Pirzadeh-Miller, S., Ellsworth, R. E., Nielsen, S. M., Russell, E. M., Beitsch, P., Esplin, E. D., Nussbaum, R. L., Pineda-Alvarez, D. E., Kurian, A. W., Hampel, H. 2023


Current guidelines recommend single gene/variant testing in relatives of patients with known pathogenic or likely pathogenic variants (PGVs) in cancer predisposition genes. This approach may preclude the use of risk-reducing strategies in family members who have PGVs in other cancer predisposition genes. Cascade testing using multigene panels was performed in 3,696 relatives of 7,433 probands. Unexpected PGVs were identified in 230 (6.2%) relatives, including 144 who were negative for the familial PGV but positive for a PGV in a different gene than the proband and 74 who tested positive for the familial PGV and had an additional PGV in a different gene than the proband. Of the relatives with unexpected PGVs, 36.3% would have qualified for different or additional cancer screening recommendations. Limiting cascade testing to only the familial PGV would have resulted in missed, actionable findings for a subset of relatives.

View details for DOI 10.1093/jnci/djad203

View details for PubMedID 37756683