Recommendations for Clinical Molecular Laboratories for Detection of Homologous Recombination Deficiency in Cancer: A Joint Consensus Recommendation of the Association of Molecular Pathology, Association of Cancer Care Centers, and College of American Pathologists

Susan J Hsiao; Destin Black; Kelly A Devereaux; Ian S Hagemann; Lawrence J Jennings; Diana Mandelker; Vera A Paulson; Michelle Shiller; Tracy L Stockley; Eric Vail; Praveen Vikas; Anna Yemelyanova

doi:10.1016/j.jmoldx.2025.05.003

Recommendations for Clinical Molecular Laboratories for Detection of Homologous Recombination Deficiency in Cancer: A Joint Consensus Recommendation of the Association of Molecular Pathology, Association of Cancer Care Centers, and College of American Pathologists

J Mol Diagn. 2025 Jun 13:S1525-1578(25)00136-9. doi: 10.1016/j.jmoldx.2025.05.003. Online ahead of print.

Authors

Affiliations

¹ The Detection of Homologous Recombination Deficiency in Cancer Working Group of the Association for Molecular Pathology, Clinical Practice Committee, Rockville, Maryland; Columbia University Medical Center, New York, New York. Electronic address: sjh2155@cumc.columbia.edu.
² The Detection of Homologous Recombination Deficiency in Cancer Working Group of the Association for Molecular Pathology, Clinical Practice Committee, Rockville, Maryland; Willis-Knighton Medical Center, Shreveport, Louisiana.
³ The Detection of Homologous Recombination Deficiency in Cancer Working Group of the Association for Molecular Pathology, Clinical Practice Committee, Rockville, Maryland; Memorial Sloan Kettering Cancer Center, New York, New York.
⁴ The Detection of Homologous Recombination Deficiency in Cancer Working Group of the Association for Molecular Pathology, Clinical Practice Committee, Rockville, Maryland; Washington University in St. Louis, St. Louis, Missouri.
⁵ The Detection of Homologous Recombination Deficiency in Cancer Working Group of the Association for Molecular Pathology, Clinical Practice Committee, Rockville, Maryland; Northwestern University, Evanston, Illinois.
⁶ The Detection of Homologous Recombination Deficiency in Cancer Working Group of the Association for Molecular Pathology, Clinical Practice Committee, Rockville, Maryland; Department of Laboratory Medicine and Pathology, University of Washington School of Medicine, Seattle, Washington.
⁷ The Detection of Homologous Recombination Deficiency in Cancer Working Group of the Association for Molecular Pathology, Clinical Practice Committee, Rockville, Maryland; Baylor University Medical Center Cancer Center Cancer Genetics, Dallas, Texas.
⁸ The Detection of Homologous Recombination Deficiency in Cancer Working Group of the Association for Molecular Pathology, Clinical Practice Committee, Rockville, Maryland; Laboratory Medicine Program, University Health Network and University of Toronto, Toronto, Ontario.
⁹ The Detection of Homologous Recombination Deficiency in Cancer Working Group of the Association for Molecular Pathology, Clinical Practice Committee, Rockville, Maryland; Cedars-Sinai Medical Center, Los Angeles, California.
¹⁰ The Detection of Homologous Recombination Deficiency in Cancer Working Group of the Association for Molecular Pathology, Clinical Practice Committee, Rockville, Maryland; The University of Iowa Holden Comprehensive Cancer Center, Iowa City, Iowa.
¹¹ The Detection of Homologous Recombination Deficiency in Cancer Working Group of the Association for Molecular Pathology, Clinical Practice Committee, Rockville, Maryland; Department of Pathology and Laboratory Medicine, Weill Cornell Medical College, New York, New York.

PMID: 40517897
DOI: 10.1016/j.jmoldx.2025.05.003

Abstract

Homologous recombination deficiency (HRD) is a genomic feature present in some malignant neoplasms and is attributed to the failure of the homologous recombination repair pathway. Tumors with an HRD-positive status may have a distinct prognosis and/or response to therapies, including poly (ADP-ribose) polymerase inhibitors. The Association for Molecular Pathology assembled an expert panel to examine current practice and perform a scoping review of the medical literature pertaining to the molecular detection of HRD in the clinical setting. The expert panel examined the following topics: components of existing and proposed HRD and genomic instability biomarkers (including mutational signatures, loss of heterozygosity, mutations in homologous recombination repair-associated genes, and epigenetic silencing of RAD51C, BRCA1, or BRCA2); technical considerations for identifying genomic scars from tumor and germline next-generation sequencing results; guidelines on interpretation and caveats when reporting assessments of genomic instability and HRD scores; and the clinical significance of HRD. The panel formulated a set of expert consensus opinion recommendations regarding HRD assay design and validation to guide laboratories in developing HRD tests to ensure high-quality and reproducible results.

Publication types

Review