Chromosomal breakage and sister chromatid exchange analysis in breast cancer patients with heterozygous BLM gene variants

Abstract Objectives BLM , a member of the RecQ helicase family, plays an important role in DNA repair, and its biallelic mutations cause autosomal recessive Bloom syndrome, a disease characterized by elevated levels of sister chromatid exchange (SCE) in affected individuals and hereditary cancer susceptibility in carriers. This study aims to investigate genomic instability in breast cancer patients carrying heterozygous variants in the BLM gene. Methods Spontaneous chromosome breakage count and SCE counting were performed on newly drawn blood cultures, both spontaneous and stimulated. The spontaneous breakage count was conducted alongside control samples. In SCE analysis, 0–10 per metaphase was considered normal, 10–40 borderline, and counts above 40 were considered high. Results The study included 26 patients and one healthy control at each session. The clinical and pathological characteristics of the patients were evaluated. The analyses revealed borderline-level increased SCE rates in only one patient. No increase in spontaneous breakage count or SCE analysis was observed in other individuals compared to controls. Conclusions Increased genomic instability was not observed in the analyzed patient group. These results can lead to multiple interpretations. The variants carried in the BLM gene in the patient group may be of low pathogenicity, or increased instability compared to controls may not be necessary for heterozygous variants. Additionally, our patient group may not have been exposed to a genotoxic effect causing genomic instability. These results could also indicate a favorable position in terms of avoiding chemotherapy and radiotherapy complications.