Acceptable genetic test to confirm hereditary breast and ovarian cancer (HBOC) syndrome (BRCA1 and BRCA2 genes only). When a relative has a previously identified pathogenic BRCA1 or BRCA2 gene variant, see Familial Mutation, Targeted Sequencing (2001961).
- Patient Preparation
- Lavender (K2EDTA), Pink (K2EDTA), or Yellow (ACD Solution A or B).
- Specimen Preparation
- Transport 3 mL whole blood. (Min: 1 mL)
- Storage/Transport Temperature
- Unacceptable Conditions
- Ambient: 1 week; Refrigerated: 1 month; Frozen: 6 months
Characteristics: Female carriers of BRCA1 mutations have a breast cancer risk of 57 percent and ovarian cancer risk of 40 percent by age 70. Female carriers of BRCA2 mutations have a breast cancer risk of 49 percent and ovarian cancer risk of 18 percent by age 70. BRCA1 mutation carriers may also be at increased risk for fallopian, peritoneal, cervical, uterine, and pancreatic cancer. BRCA2 mutation carriers may be at increased risk for pancreatic, stomach, gallbladder, bile duct, and melanoma cancers. Men with BRCA1 mutations are at increased risk for breast cancer and possibly pancreatic, prostate, and testicular cancers while male carriers of BRCA2 mutations are at increased risk for breast, pancreatic and prostate cancers.
Prevalence: 1 in 500 individuals has a BRCA1 or BRCA2 mutation; 5-10 percent of breast cancer and 10-15 percent of ovarian cancer are caused by germline BRCA1 or BRCA2 mutations.
Inheritance: Autosomal dominant.
Cause: Pathogenic germline mutations in several genes cause hereditary breast and ovarian cancer (HBOC) syndrome. Mutations in tumor suppressor genes, BRCA1 and BRCA2, are causative for 20-60 percent of HBOC.
Genes Tested: BRCA1 and BRCA2.
Clinical Sensitivity: Approximately 90 percent of BRCA1 and BRCA2 mutations.
Methodology: Bidirectional sequencing of the entire BRCA1 and BRCA2 coding regions and intron-exon boundaries.
Analytical Sensitivity and Specificity: 99 percent.
Limitations: BRCA1 and BRCA2 gene regulatory region mutations, deep intronic mutations, and large deletions/duplications will not be detected. Other genes causing HBOC are not tested. Rare diagnostic errors can occur due to primer site mutations. This assay is not designed to detect somatic variants associated with malignancy. Interpretation of this test result may be impacted if the patient has had an allogeneic stem cell transplantation.
Counseling and informed consent are recommended for genetic testing. Consent forms are available online.
|Component Test Code*||Component Chart Name||LOINC|
|2011955||BRCA Sequencing Specimen||31208-2|
|2011956||BRCA Sequencing Interpretation||59041-4|