Significant clinical impact of recurrent BRCA1 and BRCA2 mutations in Mexico

Cancer. 2015 Feb 1;121(3):372-8. doi: 10.1002/cncr.29058. Epub 2014 Sep 18.


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.

Keywords: BRCA1; BRCA2; HISPANEL; Hispanics; Mexico; Puebla; breast cancer; genetics; ovarian cancer.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • BRCA1 Protein / genetics
  • BRCA2 Protein / genetics
  • Breast Neoplasms / blood
  • Breast Neoplasms / epidemiology
  • Breast Neoplasms / genetics*
  • Female
  • Genes, BRCA1*
  • Genes, BRCA2*
  • Humans
  • Mexico / epidemiology
  • Middle Aged
  • Mutation*
  • Ovarian Neoplasms / blood
  • Ovarian Neoplasms / epidemiology
  • Ovarian Neoplasms / genetics*
  • Young Adult


  • BRCA1 Protein
  • BRCA1 protein, human
  • BRCA2 Protein
  • BRCA2 protein, human