AUTHOR=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 

TITLE=Latin American Study of Hereditary Breast and Ovarian Cancer LACAM: A Genomic Epidemiology Approach

JOURNAL=Frontiers in Oncology

VOLUME=9

YEAR=2019

URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2019.01429

DOI=10.3389/fonc.2019.01429

ISSN=2234-943X

ABSTRACT=<p><bold>Purpose:</bold> 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.</p><p><bold>Methods:</bold> 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.</p><p><bold>Results:</bold> 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 <italic>BRCA1</italic> (20%) and <italic>BRCA2</italic> (29%) genes. Pathogenic variants were found in other 12 genes, including high and moderate risk genes such as <italic>MSH2, MSH6, MUTYH</italic>, and <italic>PALB2</italic>. Additional pathogenic variants were found in HBOC unrelated genes such as <italic>DCLRE1C, WRN, PDE11A</italic>, and <italic>PDGFB</italic>.</p><p><bold>Conclusion:</bold> 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.</p>