Alemar Bárbara, Herzog Josef, Brinckmann Oliveira Netto Cristina, Artigalás Osvaldo, Schwartz Ida Vanessa D, Matzenbacher Bittar Camila, Ashton-Prolla Patricia, Weitzel Jeffrey N
Programa de Pós-graduação em Genética e Biologia Molecular (PPGBM), Universidade Federal do Rio Grande do Sul (UFRGS), Av. Bento Gonçalves, 9500-Prédio 43323M, Porto Alegre, Rio Grande do Sul 91501-970, Brazil; Laboratório de Medicina Genômica, Centro de Pesquisa Experimental, Hospital de Clínicas de Porto Alegre (HCPA), Rua Ramiro Barcelos, 2350, Porto Alegre, Rio Grande do Sul 90035-903, Brazil.
Department of Population Sciences, Division of Clinical Cancer Genetics, City of Hope, 1500 East Duarte Road, Duarte, CA 91010, USA.
Cancer Genet. 2016 Sep;209(9):417-422. doi: 10.1016/j.cancergen.2016.06.008. Epub 2016 Jun 20.
Germline mutations in BRCA1 or BRCA2 (BRCA) are responsible for 5-15% of breast (BC) and ovarian cancers (OC), predisposing to the development of early onset and often multiple primary tumors. Since mutation carriers can benefit from risk-reducing interventions, the identification of individuals with hereditary breast and ovarian cancer (HBOC) syndrome has a significant clinical impact. We assessed whether a panel assay for recurrent Hispanic BRCA mutations (HISPANEL) has an adequate breadth of coverage to be suitable as a cost effective screening tool for HBOC in a cohort of patients from Southern Brazil. A multiplex, PCR-based panel was used to genotype 232 unrelated patients for 114 germline BRCA mutations, finding deleterious mutations in 3.5% of them. This mutation prevalence is within the range detected by the HISPANEL among BC patients unselected for family history in other Latin American settings. The HISPANEL would have accounted for 27% of the BRCA mutations detected by complete sequencing in a comparison cohort (n = 193). This prevalence may be region-specific since significant differences in population structure exist in Brazil. Comprehensive analysis of BRCA in a larger set of HBOC patients from different Brazilian regions is warranted, and the results could inform customization of the HISPANEL as an affordable mutation screening tool.
BRCA1或BRCA2（BRCA）基因的种系突变导致5%-15%的乳腺癌（BC）和卵巢癌（OC），易引发早发性且通常为多发性原发性肿瘤。由于突变携带者可从降低风险的干预措施中获益，因此识别遗传性乳腺癌和卵巢癌（HBOC）综合征患者具有重大临床意义。我们评估了一种针对西班牙裔BRCA复发性突变的检测方法（HISPANEL）是否具有足够广泛的覆盖范围，以作为巴西南部一组患者中HBOC的经济有效筛查工具。使用基于PCR的多重检测方法对232名无亲缘关系的患者进行114种BRCA种系突变的基因分型，发现其中3.5%的患者存在有害突变。这种突变患病率在其他拉丁美洲地区未根据家族史选择的BC患者中，HISPANEL检测到的范围内。在一个比较队列（n = 193）中，HISPANEL可检测出通过全测序检测到的BRCA突变的27%。由于巴西人群结构存在显著差异，这种患病率可能具有区域特异性。有必要对来自巴西不同地区更大规模的HBOC患者进行BRCA综合分析，其结果可为定制HISPANEL作为一种经济实惠的突变筛查工具提供参考。
