Genetic testing for breast and ovarian cancer can be like looking for a needle in a haystack, because scientists are dealing with two extremely large genes — called BRCA1 and BRCA2 — and hundreds of possible mutations.
Testing people of Ashkenazi Jewish descent, however, is somewhat simplified. Scientists know that 80 to 90 percent of the time in Ashkenazi Jewish families with a pattern of hereditary breast and ovarian cancer, one of three specific BRCA mutations will be found.
As a result, they have developed a test that only looks for these three mutations, rather than the hundreds that can be associated with breast and ovarian cancer in general.
The Multisite Test
Interpreting the Results
Limitations of Multisite Analysis
The Multisite Test
This test, called multisite analysis, looks exclusively for three mutations in the BRCA1 and BRCA2. The mutations are named after their location on the BRCA genes. They are called:
- BRCA1.185delAG
- BRCA1.5382insC
- BRCA2.6147delT
Since this test only examines the exact locations on the BRCA genes where mutations are known to occur, it is quick and inexpensive compared to alternative tests, such as sequencing both BRCA1 and BRCA2.
Multisite analysis is only recommended for people of Ashkenazi Jewish descent because it is so specific: it will only detect the three mutations linked to breast and ovarian cancer in Ashkenazi Jewish families with hereditary cancer.
For people with other ethnic backgrounds, this test would not provide useful results. This is because there are hundreds of BRCA mutations associated with breast and ovarian cancer in the general population — and just taking a multisite test would narrow the testing process prematurely.
Interpreting Your Results
Multisite testing gives either a positive result or a negative result. There are no ambiguous results.
- Positive Result. The test has detected one of the three BRCA mutations listed above. The person being tested has inherited a mutation associated with hereditary breast and ovarian cancer in people of Ashkenazi Jewish descent, and so has an increased risk for these diseases.
- Negative Result. The test has not detected one the three mutations. The person being tested has not inherited one of the three BRCA mutations. However this result does not rule out the less likely possibility that this person could have a mutation somewhere else on the BRCA genes.
Limitations of Multisite Analysis
Multisite analysis is targeted: it detects the three mutations that account for around 80 to 90 percent of all hereditary breast and ovarian cancer in people of Ashkenazi Jewish descent.
The limitation of this test, then, is that it does not detect any of the hundreds of other mutations that have been associated with hereditary breast and ovarian cancer in the broader population.
This means that a woman who tests negative via multisite analysis cannot absolutely assume she's free of a mutation — or the increased cancer risk that goes with a mutation. She simply knows that she doesn't have one of the mutations associated with most of these cancers in people of similar ancestry.
For this reason, some people who test negative with this test decide to have full sequence analysis as a follow-up.
Read More: One Family's Experience — Multisite Testing
References:
Beller, U.D. et al. (1997). High frequency of BRCA1 and BRCA2 germline mutations in Ashkenazi Jewish ovarian cancer patients, regardless of family history [see comments]. Gynecol Oncol 67(2): 123-6.
Biesecker, B.B. and Brody, L.C. (1997). Genetic susceptibility testing for breast and ovarian cancer: a progress report. J Am Med Womens Assoc 52(1): 22-7.
Myriad (2000). Multisite analysis of three founder mutations in Ashkenazi population accounts for 90% of inherited mutations in this population. K. Fergus. San Francisco, Myriad.
Phillips, K. A. et al. (2000). Perceptions of Ashkenazi Jewish breast cancer patients on genetic testing for mutations in BRCA1 and BRCA2. Clin Genet 57(5): 376-83.
Roa, B.B. et al. (1996). Ashkenazi Jewish population frequencies for common mutations in BRCA1 and BRCA2. Nat Genet. 14:188-90.
Shattuck-Eidens, D.A. et al. (1997). BRCA1 sequence analysis in women at high risk for susceptibility mutations. Risk factor analysis and implications for genetic testing. JAMA 278(15): 1242-50.
Strewing, J.P. et al (1995) The carrier frequency of the BRCA1 185delAG mutation is approximately 1 percent in Ashkenazi Jewish individuals. Nat Genet 11:198-200.
