Patient history. Rare genetic mutation
News10-15% of cases of malignant neoplasms of the breast are associated with heredity. Up to 30-50% of them are inherited by mutations in the BRCA1 and BRCA2genes .
- The risk of developing breast cancer (breast cancer) with a mutation in these genes, according to various sources, reaches 80-90% during life.
- For this reason, the diagnosis of the BRCA1 and BRCA2 genes is recommended at the first stage of the study if a hereditary form of breast cancer is suspected.
For the Russian population, the most frequent mutations in certain 8 points of the BRCA1 and BRCA2 genes included in the basic diagnostic scopeare known .
- It is performed by PCR and covers no more than 85% of all mutations in these genes.
But in some cases, there are rare inherited mutations, and for their diagnosis, it is recommended to study the entire structure of the BRCA1 and BRCA2 genes.
Patient History
A 55-year-old patient P. turned to the center for Personalized medicine of the MCSC. Previously, she was diagnosed with metachronous primary multiple malignancies (PMZN) of the mammary glands.
- In 2008, she was diagnosed with cancer of the right breast. She underwent a combination treatment, after which she went into remission.
- In 2017, he was diagnosed with cancer of the left breast. The patient underwent surgical treatment, but in November 2019, the disease returned.
In an interview with the Center's geneticist, the patient said that her father and his sister had pancreatic cancer at the age of 62 and 55, respectively.
Taking into account the fact that the first case of breast cancer in the patient occurred at a young age, the diagnosis of PMZN and the burden of family history, she underwent a molecular genetic study of the most frequent mutations in the BRCA1 and BRCA2 genes to exclude hereditary pathology.
- But as a result of this study, no changes were found in the studied genes .
In the future, the BRCA1 and BRCA2 genes were studied by the NGS method (mass parallel sequencing, eng. Next Generation Sequencing).
- This is a modern method of DNA diagnostics, which allows you to simultaneously examine a large number of genes from beginning to end, i.e. their entire structure.
- It can be used to identify rarer genetic variants (mutations).
As a result, geneticists found that the BRCA2 gene contains a mutation c.3468delT (p.E1157Rfs*10) that was not previously described in international databases of population frequencies.
- By all indications, it was she who caused the occurrence of malignant tumors in our patient in both cases.
The main function of the BRCA1 and BRCA2 genes is to detect and remove errorsthat occur in the structure of DNA. When these genes are disrupted, such errors are not removed, and, accumulating, lead to increased risks of developing breast malignancies.
The variant (mutation) detected in our patient leads to a violation of the BRCA2 gene.
- Based on the results obtained, the patient was diagnosed with hereditary BRCA2-associated cancer of the right and left mammary glands.
- She was assigned an individual treatment and prevention plan, and recommended DNA diagnostics of relatives of the I - II degree of kinship.
The NGS method allows you to detect previously undiagnosed mutations. This contributes to the expansion of therapeutic opportunities in patients with the disease and prevention in patients who carry the mutation.
Today, both methods can be performed in the MCSC according to the CHI. To do this, you need to get a referral on the form 057/y in the polyclinic at your place of residence.
