Last update: 05/06/2006
Background to disease
OMIM # 114480
Gene OMIM 113705 (BRCA1) 600185 (BRCA2)
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 mutations. Missense mutations identified in screening of BRCA1 and BRCA2 pose a problem due to the limited knowledge regarding the functional role of the respective proteins.
Laboratory Analysis
Contact scientists. Ruth Charlton, Shahnaz Bibi, Donna Billingham
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Test |
Target reporting time (working days) |
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1. |
BRCA1: sequencing of coding region and MLPA dosage analysis |
40 (please contact laboratory before referral) |
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2. |
BRCA2: PTT of exon 11, sequencing of remaining coding region and MLPA dosage analysis |
40 (please contact laboratory before referral) |
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3. |
Predictive or confirmation testing of known mutation |
10 |