Characteristics of the test :  (includes 6 mutations in 2 genes)

 6 most common mutations in BRCA1 (OMIM# 113705) and BRCA2 (OMIM# 600185) genes – c.181T>G (p.Cys61Gly);  c.2019delA (p.Glu673Aspfsc);  c.52635264insC (p.Gln1756Profs);  c.58515854delAGTT (p.Leu1908Trpfs);  c.57185719delCT (p.Leu1908Argfs);  c.90979098insA (p.Thr3033Asnfs).

Basic characteristics of the clinical phenotype:

Relatives have been found to suffer from the same diseases such as diabetes, allergies, heart disease, cancer and more.  Carcinomas are multifactorial diseases, for the development of which both of genetic factors and environmental factors have a role.  Age, body weight, lifestyle, hormonal and dietary factors, ionizing radiation and environmental pollutants are only some of the predisposing environmental factors for the development of oncological diseases.

Mutations in the BRCA1 and BRCA2 genes play a major role of the genetic factors, predisposing to the occurrence of breast and ovarian cancer.  These two genes are responsible for the synthesis of proteins that support the normal functioning of cells by participating in important processes, including the repair of DNA damage, the control of protein synthesis, cell division and cell death.  Based on a large number of examined patients, who identify as Bulgarian, it was found that up to 70% of the mutations in BRCA1 and BRCA2 genes are located in six precisely defined regions.  The test covers specific regions in the sequence and, if negative, cannot completely rule out or confirm the role of the BRCA1 and BRCA2 genes as a factor in the development of hereditary breast and ovarian cancer.

Indications  for Referral:

• Early onset of the disease (under 45 years of age);

• Several relatives affected by breast and/or ovarian cancer on one side of the family (maternal or paternal);

• Bilateral breast cancer (both breasts are affected);

• Breast and ovaries/fallopian tubes/peritoneum cancer in one family member;
  
  Several cases of breast/ovarian cancer on one side of the family (maternal or paternal) in combination with cases of one or more of the following oncological diseases: fallopian tube; peritoneal; prostate; thyroid; endometrial; pancreatic cancers; diffuse carcinoma of the stomach, leukemia, lymphoma, brain tumors;

• Men with breast cancer;
  

• Triple-Negative breast cancer;
  
  Hereditary variant of the effect.

Interpretation of results:

● Mutations in the BRCA1/ BRCA2 genes are associated with an increased risk for breast, ovarian and bilateral breast cancer;

● Recent studies show that for BRCA1 mutation carriers, the average risk of developing these cancers by age 70 is 65% (50% - 80%) for breast cancer, 32% (24% - 40%) for ovarian cancer and an average of 27% for the development of a tumor in the other breast (4). For carriers of BRCA2 mutations, the risks are respectively 55% (40% - 70%) for breast cancer, 14.5% (11% - 18%) for ovarian cancer and an average of 12% for the development of a tumor in the other breast;

● In men, the mutations in these genes are associated with an increased lifetime risk for breast cancer (1-10%) and prostate cancer, up to 39% and 1-7% risk for pancreatic cancer, as well as a known, albeit small, risk for the development of certain other types of cancer;

● In healthy women carrying BRCA1/ BRCA2 mutations, it is recommended that preventive examinations of the breasts and ovaries with ultrasound diagnostics begin at an early age (under or at the age of 25) and be performed every six months by specialist mammologists and gynecologists;

● Once a year, a breast examination with nuclear magnetic resonance is recommended, which has a better resolution than routine mammographic examination;

● In the presence of BRCA1/BRCA2 mutations, women with breast cancer should continue to have examinations of the other breast and ovaries every six months, with an annual MRI recommended again. Similar preventive breast examinations are also recommended for women carriers of BRCA1/ BRCA2 mutations diagnosed with ovarian cancer;

● In men, carriers of BRCA1/BRCA2 mutations, prophylactic examinations, including breast and prostate imaging, are recommended every 12 months after the age of 35.

Method: Sanger sequencing

The method involves bi-directional DNA sequencing of all coding exons and intron-exon boundaries of BRCA1 and BRCA2 coding genes. The laboratory offers single exon or exon pair sequencing in the patient's relatives to determine carrier status in cases where the mutation is known (Tests #182 and 183).

Sensitivity of the method: 99%

 

What does the test involve:

● DNA isolation and sample storage;

● Polymerase chain reaction of the studied sections of the BRCA1 and BRCA2 genes;

● Direct sequencing of target genes/gene regions to detect pathogenic mutations.

● Forming a written result of the genetic test;

● Diagnostic interpretation of results and genetic counseling.

 

Biological material: Venous blood or DNA isolated from venous blood.

For more information, please visit the "Biological material requirements and transport information" section.