Recommended test to confirm hereditary breast and ovarian cancer (HBOC) syndrome (BRCA1 and BRCA2 genes only). When a relative has a previously identified pathogenic sequence 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: 2 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 have 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 the majority of HBOC.
Genes Tested: BRCA1 and BRCA2.
Clinical Sensitivity: 20-60 percent of HBOC.
Methodology: Bidirectional sequencing and multiplex ligation-dependent probe amplification (MLPA) of the entire coding regions and intron-exon boundaries of the BRCA1 and BRCA2 genes.
Analytical Sensitivity and Specificity: 99 percent.
Limitations: Rare diagnostic errors can occur due to primer or probe site mutations. Regulatory region mutations and deep intronic mutations will not be detected. Genes causing HBOC syndrome, other than BRCA1 and BRCA2, are not tested. Deletion/duplication breakpoints will not be determined. 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|
|2011950||BRCA Seq, Del/Dup Specimen||31208-2|
|2011951||BRCA Seq, Del/Dup Interp||59041-4|