Fang Zhang

Homologous recombination–deficient mutation cluster in tumor suppressor RAD51C identified by comprehensive analysis of cancer variants

Mutations in homologous recombination (HR) genes, including BRCA1 , BRCA2 , and the RAD51 paralog RAD51C , predispose to tumorigenesis and sensitize cancers to DNA-damaging agents and poly(ADP ribose) polymerase inhibitors. However, ∼800 missense variants of unknown significance have been identified for RAD51C alone, impairing cancer risk assessment and therapeutic strategies. Here, we interrogated >50 RAD51C missense variants, finding that mutations in residues conserved with RAD51 strongly predicted HR deficiency and disrupted interactions with other RAD51 paralogs. A cluster of mutations was identified in and around the Walker A box that led to impairments in HR, interactions with three other RAD51 paralogs, binding to single-stranded DNA, and ATP hydrolysis. We generated structural models of the two RAD51 paralog complexes containing RAD51C, RAD51B-RAD51C-RAD51D-XRCC2 and RAD51C-XRCC3. Together with our functional and biochemical analyses, the structural models predict ATP binding at the interface of RAD51C interactions with other RAD51 paralogs, similar to interactions between monomers in RAD51 filaments, and explain the failure of RAD51C variants in binding multiple paralogs. Ovarian cancer patients with variants in this cluster showed exceptionally long survival, which may be relevant to the reversion potential of the variants. This comprehensive analysis provides a framework for RAD51C variant classification. Importantly, it also provides insight into the functioning of the RAD51 paralog complexes.

Dyadic coping in young and middle-aged women with gynecological cancer: a latent class analysis

Cancer is a shared stress that can cause psychosocial and emotional burdens for both patients and their partners. This study aimed to identify patterns of dyadic coping (DC) among young and middle-aged women with gynecological cancer and to assess between-group differences. Between June 2021 and November 2021, patients with gynecological cancer who received therapy in a tertiary-grade hospital in Shandong, China, completed questionnaires including a demographic questionnaire, the Dyadic Coping Inventory, the PROMIS-Anxiety Short Form, the PROMIS-Depression Short Form, and the revised Conflict Tactics Scale and were classified into subtypes by latent class analysis. The sample consisted of 339 patients. Approximately one-third of the patients, especially cervical cancer patients, were exposed to varying degrees of DC issues. Three patterns were identified: class 1, middle-DC group (33.6%); class 2, low-DC group (32.2%); and class 3, high-DC group (34.2%). Postmenopausal patients were more likely to be included in class 1, while patients with cervical cancer were more likely to be included in class 2 (p < 0.05). Additionally, patients in class 2 were more likely to report insufficient emotional support (p < 0.05). A positive correlation was found for social relationship domains, and a negative correlation was found for anxiety and depression (p < 0.05). The findings indicated a high prevalence of DC in young and middle-aged women with gynecological cancer. Overall, participants scored in the low-to-middle range in terms of DC levels, and patients with cervical cancer and those with insufficient emotional support were more likely to report DC issues and require additional attention.