Frequency of Rearrangements Versus Small Indels Mutations in BRCA1 and BRCA2 Genes in Turkish Patients with High Risk Breast and Ovarian Cancer

Abstract

Objective: The current rearrangement ratio of BRCA1 and BRCA2 genes is not known in the Turkish population. Rearrangements are not routinelyinvestigated in many Turkish laboratories. This creates problems and contradictions between clinics. Therefore, the aim of this study was toevaluate the distribution and frequency of rearrangements in BRCA1 and BRCA2 genes in high-risk families and to clarify the limits of BRCA1 andBRCA2 testing in Turkey.Materials and Methods: The study included 1809 patients at high risk of breast cancer or ovarian cancer. All patients were investigated for bothsmall indels and rearrangements of BRCA genes using DNA sequencing and multiplex ligation-dependent probe amplification (MLPA) analysis.Results: The overall frequency of rearrangements was 2% (25/1262). The frequency of rearrangements was 1.7% (18/1086) and 4% (9/206) inpatients with breast cancer and ovarian cancer, respectively. The frequency of rearrangements was 3.7% (8/215) in patients with triple-negative breastcancer. The rearrangement rate was 7.7% (2/26) in patients with both breast and ovarian cancer.Conclusions: Rearrangements were found with high rates and were strongly associated with bilateral and triple-negative status of patients withbreast cancer, which are signs of high risk for breast and ovarian cancer. Analysis of rearrangements should definitely be included in routine clinicalpractice in Turkey for high-risk families and also for improved cancer risk prediction for families.