Breast cancer is the most common malignancy in women with a cumulative lifetime risk of 12% by age 70. Between 5 – 10 % of breast / ovarian cancer is due to the autosomal dominant inheritance of highly penetrant genes- ~ 1300 new cases per year in the United Kingdom. Inheritance of a mutation in the BRCA1 gene confers a lifetime risk of up to 87% of developing breast cancer and a 60 % risk of developing ovarian cancer. Approximately 95% of breast / ovarian and 45% of breast cancer only families that display an autosomal dominant pattern of inheritance are thought to be attributable to germline mutations of the BRCA1 gene.
BRCA2 mutation carriers have a similar increased risk for breast cancer and an elevated risk of male breast cancer. BRCA1 was not thought to be involved in families with male breast cancer but several cases have been identified and shown to carry a germline mutation. In addition to breast cancer, BRCA2 pedigrees contain examples of several other cancers most notably pancreatic cancer. BRCA2 is predicted to account for approximately 70% of breast cancer families shown not to be linked to 17q21 or to carry a BRCA1 mutation.
The majority of mutations identified to date in both BRCA1 and BRCA2 have been frameshift or nonsense mutations that lead to the production of a protein product with a premature termination. In addition several splice site mutations have also been identified which also lead to aberrant protein products. Various neutral polymorphisms have been identified along with several rare ‘variants’ and definite missense sequence variants. Missense changes identified in the screening of BRCA1 and BRCA2 pose a problem due to the limited knowledge regarding the functional role of the respective proteins.
All patients should be referred with the appropriate counselling services in place, for further information please contact Lab 21.
Information for test processing
To request BRCA testing, the first point of contact is the dedicated Lab 21 Customer Services Team who handle:
- Test Requests and Customer Support
- Liaison with Sample Retention Sites for sample retrieval if required
- Reporting of the results
Two options are offered for BRCA testing:
- Diagnostic testing: sequencing of all coding regions of BRCA1 & BRCA2 and MLPA dosage analysis
- Predictive or confirmation testing (known mutations)
Lab 21 requires either whole blood or extracted DNA. Processing is carried out by next generation sequencing on the Illumina platform. This provides comprehensive sequencing of all coding regions of BRCA1 & BRCA 2 and MLPA dosage analysis.
The test turn around time is 42 working days for option 1 and 12 days for option 2. A premium service can be offered for faster turn around times, please contact our customer services team for more information.