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Prevalence of five previously reported and recurrent BRCA1 genetic rearrangement mutations in 20,000 patients from hereditary breast/ovarian cancer families
Author(s) -
Hendrickson Brant C.,
Judkins Thaddeus,
Ward Benjamin D.,
Eliason Kristilyn,
Deffenbaugh Amie E.,
Burbidge Lynn Anne,
Pyne Kristin,
Leclair Benoît,
Ward Brian E.,
Scholl Thomas
Publication year - 2005
Publication title -
genes, chromosomes and cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.754
H-Index - 119
eISSN - 1098-2264
pISSN - 1045-2257
DOI - 10.1002/gcc.20189
Subject(s) - exon , gene duplication , multiplex ligation dependent probe amplification , mutation , genetics , genetic testing , breast cancer , genetic counseling , ovarian cancer , biology , medicine , cancer , gene
Many rearrangement mutations in the BRCA1 gene have been identified. It is becoming clear that some of these mutations are prevalent, and therefore their detection is necessary in order for clinical genetic tests to have high sensitivity. Published information on particular rearrangements is frequently limited to a single patient, small groups of patients, or patients of a particular ethnicity. The objectives of this work included characterizing the prevalence of five specific rearrangement mutations in a large North American patient population. A mutation‐specific multiplex PCR assay was used for determining the prevalence of five BRCA1 rearrangement mutations that previously had been reported to occur in unrelated patients. The mutation status of these rearrangements, which came from 20,712 patients at high risk for hereditary breast and/or ovarian cancers who had submitted specimens for clinical genetic testing, is presented. The results, obtained from 2,634 mutation carriers, showed a 6‐kb duplication of exon 13, identified in 53 patients (2.01%); a 26‐kb deletion encompassing exons 14–20, detected in seven patients (0.27%); a 510‐bp deletion of exon 22, detected in 5 patients (0.19%); and a 3.4‐kb deletion of exon 13, detected in one patient (0.04%). A previously reported 7.1‐kb deletion of exons 8–9 was not found. The high frequency of the exon 13 duplication makes it the fourth most prevalent mutation in these patients. These results provide an accurate picture of the prevalence of these mutations in hereditary breast/ovarian cancer patients undergoing genetic testing in North America. © 2005 Wiley‐Liss, Inc.