Absence of the BRCA1 del (exons 9–12) mutation in breast/ovarian cancer families outside of Mexican Hispanics

Abstract

The frequency and spectrum of germ line mutations in the high-penetrance breast cancer susceptibility genes BRCA1 and BRCA2 shows considerable variation by ethnic group. Most genetic epidemiological studies of the BRCA genes have been performed among Caucasian populations [1], with the exception of a few studies involving other ethnic groups, such as Hispanics [2–4], Asians [5, 6], and African Americans [7–9]. In most of these studies only the frequencies of sequence detectable BRCA mutations were reported and large genomic rearrangements including deletions and insertions of one or more exons, which account for 6–15% of all deleterious mutations in these genes have infrequently been considered [10–12]. Most BRCA mutations are unique; however, few recurrent mutations with founder effects have been found in European, Hispanic, American and Asian populations [13]. In a recent study on Hispanic high-risk breast/ovarian cancer families of mainly Mexican descent from South California, Weitzel and colleagues reported the identification of a novel deletion of BRCA1 exons 9 through 12 using multiplex quantitative differential polymerase chain reaction (PCR) analysis. The deletion was detected in 3.8% of families negative for sequence detectable BRCA mutations [14]. The large genomic rearrangement mutation is considered deleterious as it results in loss of critical functional domains as well as premature truncation of the BRCA1 protein. Given the relatively high prevalence of the deletion in this cohort, the authors suggest to include the screening for this mutation in the genetic testing strategy in Hispanic women without sequence detectable BRCA mutations.