Aim: To implement an accessible strategy for detection of the Mexican founder mutation NG_005905.2:g.118973_133629del, located in BRCA1, which deletes exons 9-12 (BRCA1 ex9-12del), as part of the health care setting of patients with hereditary breast and ovarian cancer (HBOC), from the National Cancer Institute (Mexico).

Material and methods: We designed a polymerase chain reaction (PCR) based method, for the targeted detection of the deletion of exons 9 through 12, of the BRCA1 gene. The method was validated with previously verified results of the deletion by multiplex ligation-dependent probe amplification assay (MLPA), or deep sequencing of the region. Finally, the technique was used for the detection of BRCA1 ex9-12del mutation in a group of 302 HBOC patients, in whom the existence of BRCA1 and BRCA2 point mutations had been ruled by pyrosequencing.

Results: The concordance of our method, with previously reported BRCA1 ex9-12del mutation results, was 100%. Also, we provided a profile of the clinical and familial characteristics of 302 Mexican patients with clinical suspicion of HBOC, in whom the detection of BRCA1 ex9-12del mutation was performed. In this way, 21 patients (6.95%) were identified as BRCA1 ex9-12del mutation carriers. Among whom, a higher proportion of triple negative breast cancer was found (73% versus 21%, p=0.0005; two sided Fisher's exact test) .

Conclusions: A feasible molecular diagnostic strategy for the detection of BRCA1 ex9-12del mutation was established in Mexican patients, with HBOC. In this way, we identified 21 (21/302) carriers of the deletion, who represented the 6.95%. Related to the clinical features, triple negative breast cancer carriers stood out. It had been reported that large genomic rearrangements in BRCA1 are associated with an increased frequency of high risk features.

These type of approach is appropriate in populations where a founder effect is recognized. For its simplicity and effectiveness, it can be transferred to other laboratories, for the benefit of a greater number of Mexican patients and with the aim of minimize costs of testing. Because of the frequency of BRCA1 ex9-12del mutation, this method has been implemented as the first line of BRCA1 clinical genetic analysis in patients with suspected HBOC, at National Cancer Institute (Mexico ).

Citation Format: Rosa M. Alvarez, Jose Velazquez, Veronica Fragoso, Julieta Dominguez, Paulina Nuñez, Talia Wegman, Yuliana Sanchez, Silvia Vidal, Enrique Bargallo, Dolores Gallardo, Abelardo Meneses, Luis A. Herrera. Screening for BRCA1 founder mutation in Mexican population: an accessible approach [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 4278. doi:10.1158/1538-7445.AM2017-4278