A decade of RAD51C and RAD51D germline variants in cancer
Jacopo Boni1, Aida Idani1, Carla Roca1
1Program in Molecular Mechanisms and Experimental Therapy in Oncology (Oncobell), Bellvitge Biomedical Research Institute (IDIBELL), Hospitalet de Llobregat, Barcelona, Spain.
Human Mutation
|December 19, 2021
Summary
Germline pathogenic variants in RAD51C and RAD51D DNA repair genes increase cancer risk. This study catalogs 341 variants, identifies recurrent mutations, and provides an update on these cancer predisposition genes.
Area of Science:
- Genetics
- Cancer Biology
- Molecular Oncology
Background:
- Defects in DNA repair genes are linked to cancer susceptibility.
- Germline pathogenic variants (GPV) in homologous recombination repair genes predispose to breast and ovarian cancers.
- RAD51C and RAD51D are key homologous recombination repair genes associated with familial ovarian cancer.
Purpose of the Study:
- To review and catalog RAD51C and RAD51D germline variants in cancer.
- To integrate literature data with in-house patient screening results.
- To provide an updated comprehensive resource on these cancer predisposition genes.
Main Methods:
- Literature review of RAD51C and RAD51D germline variants over the past decade.
- Integration of variants from in-house patient screening.
- Classification of variants using ACMG/AMP criteria.
- Analysis of population frequencies and functional data for recurrent variants.
- Assessment of residue conservation and hotspot modeling.
Main Results:
- A comprehensive catalog of 341 RAD51C and RAD51D germline variants was generated.
- Recurrent variants in both genes were identified and characterized.
- Data on population frequencies and functional studies for recurrent variants were compiled.
- Information on uncharacterized variants was highlighted.
- Conservation analysis and hotspot modeling were performed.
Conclusions:
- This study provides an exhaustive update on RAD51C and RAD51D germline variants in cancer.
- The catalog and analysis of variants aid in understanding their role in cancer predisposition.
- Further characterization of unclassified variants is needed to establish pathogenicity.
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