Abstract P2-09-13: BRCA mutations in South Texas and the Rio Grande Valley among Hispanics with a personal or family history of breast cancer
Authors: Mette LA , Poullard NE , Pulido Saldivar AM , Torres IC , Seth SG , Seigler D , Jatoi I , Tomlinson GE 
Published: May 2016

Abstract
South Texas, including regions along the US-Mexico border, is characterized by a predominantly Hispanic population, most of who are of Mexican decent. In the past decade, the discovery of Mexican-American founder mutations in BRCA1/2 has established the importance of large rearrangement testing in this population. Recent studies estimate that 15-25% of Mexican women with early-onset breast cancer carry a BRCA mutation, with the BRCA1 EX9-12 deletion accounting for 10% of all mutations. Here we review the BRCA1/2 pathogenic and unclassified variants in our South Texas Hispanic population who underwent cancer genetic risk assessment and testing between June 2013 and May 2015. All mutation carriers had either a personal history of early-onset breast cancer (before age 50), or early-onset breast cancer in a first-degree relative. A total of 23 unique mutations were identified in 28 kindreds. Three affected individuals harbored mutations that had not previously been reported in the literature at the time of testing (BRCA1 134+3A&gt;T; BRCA2 428C&gt;G; BRCA2 8265A&gt;T). Pathogenic mutations in BRCA1 were the most common finding, accounting for 64.3% of identified variants. The BRCA1 EX9-12 deletion was only found in only family. We also identified a co-segregating pathogenic mutation (1793delA) and variant of uncertain significance (1149G&gt;A) in BRCA1 in two unrelated kindreds, suggesting a possible founder mutation. Although previous studies have identified recurrent BRCA mutations in Hispanic families with breast cancer in the Southwestern United States, this was not seen in our sample of South Texas Hispanics. While only one (3.5%) of our families had the BRCA1 EX9-12 deletion, other large rearrangements, such as BRCA1 EX1-2 deletion, BRCA1 EX21-22 duplication and whole gene deletions demonstrate the continued importance of comprehensive BRCA1/2 analysis in Hispanics. This work was supported by CPRIT Grant PP120089 and NIH 2P30CA054174.
BRCA gene mutations in South Texas Hispanics with a personal or family history of breast cancerMutation (n%)FrequencyKindredsBRCA1 pathogenic (64.3%)2715delEX1-2631793delA*42EX12del41815_824deupAGCCATGTGG31delEX9-1221entire gene deletion213878delTA11IVS16+3G-T112806_2809delAAAC11188insAG114936delG11dup21-2211BRCA2 pathogenic (9.5%)44R2520X228377G&gt;A118591G&gt;A11BRCA1 variant of uncertain significance (16.7%)751149G&gt;A*427819C&gt;T115470A&gt;G11134+3A&gt;T11BRCA2 variant of uncertain significance (9.5%)44314+12A&gt;G11428C&gt;G113575T&gt;G118265A&gt;T11*co-segregating
Citation Format: Mette LA, Poullard NE, Pulido Saldivar AM, Torres IC, Seth SG, Seigler D, Jatoi I, Tomlinson GE. BRCA mutations in South Texas and the Rio Grande Valley among Hispanics with a personal or family history of breast cancer. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P2-09-13.