Format

Send to

Choose Destination
Front Oncol. 2019 Dec 20;9:1429. doi: 10.3389/fonc.2019.01429. eCollection 2019.

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

Author information

1
Medical Oncology Service, Hospitales Universitarios Regional y Virgen de la Victoria, Institute of Biomedical Research in Malaga, CIMES, University of Málaga, Málaga, Spain.
2
Laboratorio de Secuenciación, Instituto de Medicina Traslacional e Ingeniería Biomédica, Hospital Italiano de Buenos Aires, Buenos Aires, Argentina.
3
Laboratorio Nacional en Salud, Diagnóstico Molecular y Efecto Ambiental en Enfermedades Crónico-Degenerativas, Facultad de Estudios Superiores Iztacala, Tlalnepantla de Baz, Mexico.
4
Unidad de Biomedicina, Facultad de Estudios Superiores Iztacala, UNAM, Tlalnepantla de Baz, Mexico.
5
Instituto de Nutrición, Genética y Metabolismo, Facultad de Medicina, Universidad El Bosque, Bogota, Colombia.
6
Grupo INPAC, Organización Keralty, Departamento de Genética, Clínica Universitaria Colombia, Bogotá, Colombia.
7
Grupo INPAC, Organización Keralty, Facultad de Medicina, Fundación Universitaria Sanitas, Bogotá, Colombia.
8
Servicio de Genética, Hospital Universitario San Ignacio, Bogotá, Colombia.
9
Instituto de Genética Humana, Facultad de Medicina, Pontificia Universidad Javeriana, Bogotá, Colombia.
10
Clínica Universitaria Bolivariana, Pontificia Universidad Bolivariana, Medellín, Colombia.
11
Departamento Ciencias Básicas de Salud, Facultad de Ciencias de la Salud, Pontificia Universidad Javeriana Cali, Cali, Colombia.
12
Centro Médico Imbanaco, Cali, Colombia.
13
Departamento Materno Infantil, Facultad de Ciencias de la Salud, Pontificia Universidad Javeriana Cali, Cali, Colombia.
14
Fundación Cardiovascular de Colombia, Centro de Investigaciones, Floridablanca, Colombia.
15
Departamento de Investigación y Estudios Clínicos, IMAT - Oncomédica S.A., Montería, Colombia.
16
Instituto de Medicina Traslacional e Ingeniería Biomédica, CONICET-Instituto Universitario del Hospital Italiano-Hospital Italiano de Buenos Aires, Buenos Aires, Argentina.
17
Servicio de Ginecología, Hospital Italiano de Buenos Aires, Buenos Aires, Argentina.
18
Centro Oncológico Estatal ISSEMyM, Toluca de Lerdo, Mexico.
19
INVEGEM, Guatemala, Guatemala.
20
Instituto Nacional de Salud Pública, Cuernavaca, Mexico.
21
Hubert Department of Global Health, Emory University, Atlanta, GA, United States.
22
Departamento de Oncología Médica, Instituto Nacional de Enfermedades Neoplásicas, Lima, Peru.
23
Departamento de Investigación, Instituto Nacional de Enfermedades Neoplásicas, Lima, Peru.
24
Fundación Alma, Ciudad de México, Mexico.
25
Instituto Estatal de Cancerología de Colima, Colima, Mexico.
26
Laboratorio de Investigación Biomédica, Unidad Académica de Medicina, Universidad Autónoma de Nayarit, Tepic, Mexico.
27
Instituto Mexicano del Seguro Social, Ciudad de México, Mexico.
28
Unidad de Investigación Biomédica en Cáncer, Instituto de Investigaciones Biomédicas-Instituto Nacional de Cancerología, Ciudad de México, Mexico.
29
Departamento de Patología, Hospital Universitario Fundación Santa Fe de Bogotá, Bogota, Colombia.
30
Instituto Nacional de Cancerología, Ciudad de México, Mexico.

Abstract

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

KEYWORDS:

HBOC; Latin America; breast cancer susceptibility; germline pathogenic variants; massively parallel sequencing

Supplemental Content

Full text links

Icon for Frontiers Media SA Icon for PubMed Central
Loading ...
Support Center