Detection of the 657del5 mutation in the NBS1 gene
10 days Hereditary breast cancer and ovarian cancer are considered the most common types of familial tumors. Genetic risk factors for the development of these conditions are associated with the presence of mutations in the BRCA1, BRCA2, NBS1, and CHEK2 genes. These genes encode proteins involved in the repair system of damaged DNA and the maintenance of genome stability. Defects in the NBS1 gene can lead not only to breast and ovarian cancer but also to other malignancies, including: acute lymphoblastic leukemia, non-Hodgkin lymphoma, acute myeloblastic leukemia, colorectal cancer, thyroid tumors, and prostate cancer.
NBS1 (Nijmegen Breakage Syndrome)
The NBS1 gene encodes the nibrin protein, which is involved in cell cycle regulation and plays an essential role in the repair of DNA double-strand breaks. The 657del5 mutation in the NBS1 gene is considered a moderately penetrant marker of susceptibility to breast and ovarian cancer. In its homozygous form, it is associated with the development of autosomal recessive Nijmegen chromosomal instability syndrome; in the heterozygous state, it increases chromosomal instability and the risk of developing breast cancer and other tumors.
The frequency of the 657del5 mutation in the Slavic population is 0.5–0.7%.
In the presence of this mutation, radiotherapy and chemotherapy using radiomimetic agents (e.g., bleomycin) are strictly contraindicated.
Testing is recommended for the following individuals:
- Oncology patients, to determine the hereditary nature of the disease and to improve treatment efficacy (e.g., adapting surgical strategy and drug therapy);
- Healthy relatives of cancer patients, to assess their risk of developing the disease;
- As part of screening programs, to improve early diagnosis of breast and ovarian cancer.
Indications for testing for this mutation include:
- Burdened family history: two or more cases of breast and/or ovarian cancer in first- or second-degree relatives, early-onset disease, bilateral breast cancer, male breast cancer, tumors of the same location, or rare cancer types in two or more relatives;
- Early-onset breast cancer;
- Multiple primary tumors in different organs;
- Atypical proliferative diseases of the breast;
- Specific ethnic background (e.g., Ashkenazi Jewish ancestry).
Testing Method: Real-time Polymerase Chain Reaction (PCR).
Possible Results:
N/N – deletion not detected;
N/del – deletion detected in the heterozygous state;
del/del – deletion detected in the homozygous state.
The absence of the deletion does not exclude the risk of breast cancer or other types of cancer and does not replace regular clinical evaluations (including self-examination, ultrasound, mammography, and consultation with a breast specialist, gynecologist, or oncologist), especially after the age of 35.
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