The Association for Molecular Pathology has introduced best practice recommendations for clinical laboratories developing and performing homologous recombination deficiency testing, according to new guidelines published by Hsiao et al in The Journal of Molecular Diagnostics.
Background
Homologous recombination deficiency testing is designed to identify tumors that are unable to effectively repair DNA damage through the homologous recombination repair pathway. This deficiency is often linked to increased genomic instability and serves as a potential biomarker for predicting response to certain cancer therapies.
Although multiple assays are currently available, the tests often differ in their definitions of homologous recombination deficiency, the biomarkers they assess, and the algorithms they employ. These differences may impact treatment decisions, particularly among patients who may benefit from PARP inhibitors.
Overview of New Guidelines
To develop the best practice recommendations, an expert panel comprising organizational representation from ASCO, the Association of Community Cancer Centers, and the College of American Pathologists reviewed current practices and assessed the medical literature related to the molecular detection of homologous recombination deficiency in clinical settings. The guidelines were based on survey data, a review of more than 4,300 peer-reviewed scientific publications, professional experience, and consensus of the subject matter experts.
“As part of our assessment, we identified considerable variability in many aspects of [homologous recombination deficiency] testing, including sample requirements, tumor types, molecular methodologies, and the biomarkers evaluated,” detailed Alanna J. Church, MD, Associate Director of the Laboratory for Molecular Pediatric Pathology at Dana-Farber/Boston Children’s Cancer Center as well as Chair of the Association for Molecular Pathology’s 2025 Clinical Practice Committee.
The panel developed 12 recommendations focused on the design and validation of homologous recombination deficiency assays. The recommendations addressed technical aspects of genomic instability and homologous recombination deficiency analysis—including the interpretation of genomic scars from tumor and germline next-generation sequencing results as well as the clinical relevance of homologous recombination deficiency biomarkers.
Conclusions
“This new report offers evidence-based recommendations for [homologous recombination deficiency] diagnostic assays to help improve standardization, transparency, quality across laboratories, and care for patients [with cancer],” Dr. Church emphasized.
“These recommendations are intended to guide clinical laboratories offering [homologous recombination deficiency] testing and highlight areas where further research and validation are needed,” indicated lead study author Susan Hsiao, MD, PhD, Associate Professor of Pathology and Cell Biology at the Columbia University Vagelos College of Physicians and Surgeons and Chair of the Association for Molecular Pathology’s Detection of HRD in Cancer Working Group. “[The Association for Molecular Pathology] remains committed to refining these recommendations as scientific knowledge and technology continue to evolve,” she concluded.
Disclosure: For full disclosures of the guideline authors, visit jmdjournal.org.
