Significant clinical impact of recurrent BRCA1 and BRCA2 mutations in Mexico. Issue 3 (18th September 2014)

• Record Type: Journal Article
• Authors: Villarreal‐Garza, Cynthia; Alvarez‐Gómez, Rosa María; Pérez‐Plasencia, Carlos; Herrera, Luis A.; Herzog, Josef; Castillo, Danielle; Mohar, Alejandro; Castro, Clementina; Gallardo, Lenny N.; Gallardo, Dolores; Santibáñez, Miguel; Blazer, Kathleen R.; Weitzel, Jeffrey N.
• Is Part Of: Cancer. Volume 121:Issue 3(2015)
• Page Start: 372
• Page End: 378
• Publication Date: 2014-09-18
• Subjects: Cancer -- Periodicals; Cancer -- Cytopathology -- Periodicals; 616.99405
• DOI: 10.1002/cncr.29058
• Languages: English
• ISSNs: 0008-543X

Abstract

<abstract abstract-type="main"> <title> <x xml:space="preserve">Abstract</x> </title> <sec id="cncr29058-sec-0001" sec-type="section"> <title>BACKGROUND</title> <p>Frequent recurrent mutations in the breast and ovarian cancer susceptibility (<italic>BRCA</italic>) genes <italic>BRCA1</italic> and <italic>BRCA2</italic> among Hispanics, including a large rearrangement Mexican founder mutation (<italic>BRCA1</italic> exon 9‐12 deletion [ex9‐12del]), suggest that an ancestry‐informed <italic>BRCA</italic>‐testing strategy could reduce disparities and promote cancer prevention by enabling economic screening for hereditary breast and ovarian cancer in Mexico.</p> </sec> <sec id="cncr29058-sec-0002" sec-type="section"> <title>METHODS</title> <p>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 <italic>BRCA</italic> 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 <italic>BRCA1</italic> ex9‐12del mutation). This was followed by sequencing of all <italic>BRCA</italic> exons and adjacent intronic regions and a <italic>BRCA1</italic> multiplex ligation‐dependent probe amplification assay (MLPA) for HISPANEL‐negative patients. <italic>BRCA</italic> mutation prevalence was calculated and correlated with histology and tumor receptor status, and HISPANEL sensitivity was estimated.</p> </sec> <sec id="cncr29058-sec-0003" sec-type="section"> <title>RESULTS</title> <p> <italic>BRCA</italic> 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 (<italic>BRCA1</italic> ex9‐12del) accounted for 35% of <italic>BRCA</italic>‐associated ovarian cancers and 29% of <italic>BRCA</italic>‐associated breast cancers. At 2% of the sequencing and MLPA cost, HISPANEL detected 68% of all <italic>BRCA</italic> mutations.</p> </sec> <sec id="cncr29058-sec-0004" sec-type="section"> <title>CONCLUSIONS</title> <p>In this study, a remarkably high prevalence of <italic>BRCA</italic> mutations was observed among patients with ovarian cancer and breast cancer who were not selected for family history, and the <italic>BRCA1</italic> ex9‐12del mutation explained 33% of the total. The remarkable frequency of <italic>BRCA1</italic> 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. <bold><italic>Cancer</italic> 2015;121:372–378.</bold> © <italic>2014 American Cancer Society</italic>.</p> </sec> </abstract>