Özet:

Objective: Although the molecular etiology of breast cancer is not clearly known, hereditary genetic causes are responsible for approximately 10%. In addition to BRCA1 and BRCA2 genes, there are many genes that cause breast cancer. In this study, we performed a hereditary cancer genetic panel test among hereditary breast cancer patients who are negative for BRCA1 and BRCA2 genes. Accordingly, the frequency of mutations, causing hereditary cancer among Turkish breast cancer patients, was investigated. Method: All the 70 patients were unrelated and provided BRCA testing criteria according to the National Comprehensive Cancer Network guidelines, but they were reported as unfavorable. Qiagen large hereditary cancer panel and Hereditary Cancer Solution v1.1 panel were used for sequencing. The sequencing process was performed on the Illumina MiSeq system. The data analyses were performed on QIAGEN Clinical Insight (QCI™) Analyze software and Sophia DDM software. Results: Of 70 patients, 6 (8.5%) were found to carry a pathogenic, and 1 (1.4%) were found to give a likely pathogenic mutation. Pathogenic variants were detected in ATM, NBN, PTEN, RAD51C genes; the likely pathogenic variant was discovered in the MUTYH gene. Only, PTEN:c.407G>A mutation was found in two patients; the other mutations were detected once in each patient. A nonsense alteration, RAD51C:c.907G>T, was described as novel variant. The variant of uncertain significance variants was detected in 10 patients (14.2%). Conclusions: It is essential to perform the hereditary cancer panel from index cases in families with high cancer incidence, whose BRCA1/2 negative and molecular background has not been elucidated, for preventive health policies. In addition, the identification of common familial cancer genes will guide personalized therapy planning.

Anahtar Kelimeler: