Send to

Choose Destination
See comment in PubMed Commons below
J Mol Diagn. 2009 May;11(3):176-81. doi: 10.2353/jmoldx.2009.080137. Epub 2009 Mar 26.

A rapid and reliable test for BRCA1 and BRCA2 founder mutation analysis in paraffin tissue using pyrosequencing.

Author information

  • 1Department of Pathology, Memorial Sloan-Kettering Cancer Center, New York, New York 10065, USA.


The founder mutations in BRCA (BRCA1*185delAG, BRCA1*5382insC, and BRCA2*6174delT) account for 95% of the detectable BRCA mutations in breast and ovarian cancer families of Ashkenazi Jewish ancestry. Optimal clinical management of individuals from these high-risk families relies on the identification of BRCA founder mutations in the laboratory. We have therefore developed a rapid and reliable approach using pyrosequencing, which allows for the detection of these frequent frameshift mutations on different types of specimens. We were able to correctly identify all mutants in a blinded analysis of 177 DNA samples, including 120 DNA samples extracted from paraffin tissues, 30 samples derived from blood specimens, and 27 samples derived from saliva. The mutation detection rate of pyrosequencing was 100% for all of the DNA samples tested with neither false-positive nor false-negative results. The assay also demonstrated both high accuracy and high precision for the detection of these common mutations in paraffin tissues. Furthermore, saliva collection is a noninvasive alternative for DNA isolation in both clinical and research settings. We show that pyrosequencing is a rapid and reliable method that serves as an excellent platform for BRCA founder mutation analysis, especially when only paraffin-embedded tissues are available.

[PubMed - indexed for MEDLINE]
Free PMC Article
PubMed Commons home

PubMed Commons

How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Elsevier Science Icon for PubMed Central
    Loading ...
    Write to the Help Desk