RAD51 – Hereditary Breast Carcinoma

A germline variant in RAD51 (HGNC:9817) has been implicated in hereditary breast carcinoma (MONDO:0016419) through targeted mutation screening. In a Japanese cohort study, two unrelated patients with synchronous bilateral breast cancer were found to carry the RAD51 c.449G>A (p.Arg150Gln) missense change, absent in 100 control individuals (2 probands [PMID:10807537]). No additional segregation data or recurrent observations have been reported, limiting the genetic evidence to these two cases without family-based co-segregation. RAD51 encodes a recombinase critical for homologous recombination repair and interacts with BRCA1/2 to resolve DNA double-strand breaks. Functional assays in mammalian cells demonstrate that perturbation of RAD51 ATP hydrolysis impairs homology-directed repair, supporting a loss-of-function mechanism for disease predisposition ([PMID:11923292]). However, no direct functional assessment of the p.Arg150Gln variant has been performed. No conflicting studies have emerged, but the low number of observations and absence of segregation or replication require cautious interpretation.

Key Take-home: The RAD51 c.449G>A (p.Arg150Gln) variant may contribute to hereditary breast carcinoma risk, but further familial and functional studies are necessary to establish clinical validity and utility.

References

• Journal of human genetics • 2000 • Identification of Rad51 alteration in patients with bilateral breast cancer. PMID:10807537
• The Journal of biological chemistry • 2002 • ATP hydrolysis by mammalian RAD51 has a key role during homology-directed DNA repair. PMID:11923292

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