Oliver Javier, Quezada Urban Rosalía, Franco Cortés Claudia Alejandra, Díaz Velásquez Clara Estela, Montealegre Paez Ana Lorena, Pacheco-Orozco Rafael Adrián, Castro Rojas Carlos, García-Robles Reggie, López Rivera Juan Javier, Gaitán Chaparro Sandra, Gómez Ana Milena, Suarez Obando Fernando, Giraldo Gustavo, Maya Maria Isabel, Hurtado-Villa Paula, Sanchez Ana Isabel, Serrano Norma, Orduz Galvis Ana Isabel, Aruachan Sandra, Nuñez Castillo Johanna, Frecha Cecilia, Riggi Cecilia, Jauk Federico, Gómez García Eva María, Carranza Claudia Lorena, Zamora Vanessa, Torres Mejía Gabriela, Romieu Isabelle, Castañeda Carlos Arturo, Castillo Miluska, Gitler Rina, Antoniano Adriana, Rojas Jiménez Ernesto, Romero Cruz Luis Enrique, Vallejo Lecuona Fernando, Delgado Enciso Iván, Martínez Rizo Abril Bernardette, Flores Carranza Alejandro, Benites Godinez Verónica, Méndez Catalá Claudia Fabiola, Herrera Luis Alonso, Chirino Yolanda Irasema, Terrazas Luis Ignacio, Perdomo Sandra, Vaca Paniagua Felipe
Medical Oncology Service, Hospitales Universitarios Regional y Virgen de la Victoria, Institute of Biomedical Research in Malaga, CIMES, University of Málaga, Málaga, Spain.
Laboratorio de Secuenciación, Instituto de Medicina Traslacional e Ingeniería Biomédica, Hospital Italiano de Buenos Aires, Buenos Aires, Argentina.
Front Oncol. 2019 Dec 20;9:1429. doi: 10.3389/fonc.2019.01429. eCollection 2019.
Hereditary Breast and Ovarian Cancer (HBOC) syndrome is responsible for ~5-10% of all diagnosed breast and ovarian cancers. Breast cancer is the most common malignancy and the leading cause of cancer-related mortality among women in Latin America (LA). The main objective of this study was to develop a comprehensive understanding of the genomic epidemiology of HBOC throughout the establishment of The Latin American consortium for HBOC-LACAM, consisting of specialists from 5 countries in LA and the description of the genomic results from the first phase of the study. We have recruited 403 individuals that fulfilled the criteria for HBOC from 11 health institutions of Argentina, Colombia, Guatemala, Mexico and Peru. A pilot cohort of 222 individuals was analyzed by NGS gene panels. One hundred forty-three genes were selected on the basis of their putative role in susceptibility to different hereditary cancers. Libraries were sequenced in MiSeq (Illumina, Inc.) and PGM (Ion Torrent-Thermo Fisher Scientific) platforms. The overall prevalence of pathogenic variants was 17% (38/222); the distribution spanned 14 genes and varied by country. The highest relative prevalence of pathogenic variants was found in patients from Argentina (25%, 14/57), followed by Mexico (18%, 12/68), Guatemala (16%, 3/19), and Colombia (13%, 10/78). Pathogenic variants were found in (20%) and (29%) genes. Pathogenic variants were found in other 12 genes, including high and moderate risk genes such as , and . Additional pathogenic variants were found in HBOC unrelated genes such as , and . In this first phase of the project, we recruited 403 individuals and evaluated the germline genetic alterations in an initial cohort of 222 patients among 4 countries. Our data show for the first time in LA the distribution of pathogenic variants in a broad set of cancer susceptibility genes in HBOC. Even though we used extended gene panels, there was still a high proportion of patients without any detectable pathogenic variant, which emphasizes the larger, unexplored genetic nature of the disease in these populations.
遗传性乳腺癌和卵巢癌（HBOC）综合征导致了约5%-10%的所有确诊乳腺癌和卵巢癌。乳腺癌是拉丁美洲（LA）女性中最常见的恶性肿瘤以及癌症相关死亡的主要原因。本研究的主要目的是通过建立由拉丁美洲5个国家的专家组成的HBOC拉丁美洲联盟（LACAM），全面了解HBOC的基因组流行病学，并描述该研究第一阶段的基因组结果。我们从阿根廷、哥伦比亚、危地马拉、墨西哥和秘鲁的11个卫生机构招募了403名符合HBOC标准的个体。对222名个体的试点队列进行了二代测序（NGS）基因检测板分析。根据143个基因在不同遗传性癌症易感性中的假定作用进行选择。文库在MiSeq（Illumina公司）和PGM（Ion Torrent-赛默飞世尔科技公司）平台上进行测序。致病变异的总体患病率为17%（38/222）；分布在14个基因中，且因国家而异。致病变异相对患病率最高的是来自阿根廷的患者（25%，14/57），其次是墨西哥（18%，12/68）、危地马拉（16%，3/19）和哥伦比亚（13%，10/78）。在 （20%）和 （29%）基因中发现了致病变异。在其他12个基因中发现了致病变异，包括高风险和中度风险基因，如 、 和 。在与HBOC无关的基因如 、 和 中也发现了其他致病变异。在该项目的第一阶段，我们招募了403名个体，并评估了4个国家中222名患者初始队列中的种系基因改变。我们的数据首次在拉丁美洲展示了HBOC中广泛的癌症易感基因中致病变异的分布。尽管我们使用了扩展基因检测板，但仍有很大比例的患者没有任何可检测到的致病变异，这强调了这些人群中该疾病尚未被探索的更大的遗传本质。
