BRCA 1 mutation site may be linked with nuclear DNA ploidy in BRCA 1 ‐mutated ovarian carcinomas

Aims BRCA 1 has a role in maintaining normal nuclear DNA content during cell division and its inactivation may result in DNA aneuploidy and cancer progression. BRCA 1 ‐linked breast cancers are more aneuploid and have a worse prognosis, but this has not been elucidated in ovarian cancers. This study explores the potential difference in ploidy status between BRCA 1 ‐mutated and sporadic ovarian carcinomas. It also explores the potential association between BRCA 1 mutation site and DNA ploidy status. Methods This study compared DNA ploidy status of tumor blocks from 23 BRCA 1 ‐mutated ovarian carcinomas with that of 23 sporadic ovarian carcinomas matched for histologic subtype, patient age, stage and grade. DNA content of the nuclei was measured by F eulgen– S chiff staining followed by image cytometry and compared. Results BRCA 1 ‐linked tumors with a stop codon closer to the N ‐terminal (between 1 and 500 aa; 6/6, 100%) had a significantly higher frequency of nondiploidy compared with those with stop codon above 500 aa (7/12, 58%) ( P  = 0.033). A diploid peak was detected in 28% of BRCA 1 ‐mutated ovarian cancers and in 33% of sporadic ovarian cancers. Conclusions The present study concluded that ovarian tumors with mutations closer to the N ‐terminal of BRCA 1 may have a higher risk of DNA aneuploidy. There is no significant difference between BRCA 1 ‐mutated and sporadic ovarian carcinomas with respect to the DNA content.