BACKGROUND: Frequent recurrent mutations in the breast and ovarian cancer 
susceptibility (BRCA) genes BRCA1 and BRCA2 among Hispanics, including a large 
rearrangement Mexican founder mutation (BRCA1 exon 9-12 deletion [ex9-12del]), 
suggest that an ancestry-informed BRCA-testing strategy could reduce disparities 
and promote cancer prevention by enabling economic screening for hereditary 
breast and ovarian cancer in Mexico.
METHODS: In a multistage approach, 188 patients with cancer who were unselected 
for family cancer history (92 with ovarian cancer and 96 with breast cancer) 
were screened for BRCA mutations using a Hispanic mutation panel (HISPANEL) of 
115 recurrent mutations in a multiplex assay (114 were screened on a mass 
spectroscopy platform, and a polymerase chain reaction assay was used to screen 
for the BRCA1 ex9-12del mutation). This was followed by sequencing of all BRCA 
exons and adjacent intronic regions and a BRCA1 multiplex ligation-dependent 
probe amplification assay (MLPA) for HISPANEL-negative patients. BRCA mutation 
prevalence was calculated and correlated with histology and tumor receptor 
status, and HISPANEL sensitivity was estimated.
RESULTS: BRCA mutations were detected in 26 of 92 patients (28%) with ovarian 
cancer, in 14 of 96 patients (15%) with breast cancer overall, and in 9 of 33 
patients (27%) who had tumors that were negative for estrogen receptor, 
progesterone receptor, and human epithelial growth factor 2 (triple-negative 
breast cancer). Most patients with breast cancer were diagnosed with locally 
advanced disease. The Mexican founder mutation (BRCA1 ex9-12del) accounted for 
35% of BRCA-associated ovarian cancers and 29% of BRCA-associated breast 
cancers. At 2% of the sequencing and MLPA cost, HISPANEL detected 68% of all 
BRCA mutations.
CONCLUSIONS: In this study, a remarkably high prevalence of BRCA mutations was 
observed among patients with ovarian cancer and breast cancer who were not 
selected for family history, and the BRCA1 ex9-12del mutation explained 33% of 
the total. The remarkable frequency of BRCA1 ex9-12del in Mexico City supports a 
nearby origin of this Mexican founder mutation and may constitute a regional 
public health problem. The HISPANEL mutation panel presents a translational 
opportunity for cost-effective genetic testing to enable breast and ovarian 
cancer prevention.