Send to

Choose Destination

See 1 citation found by title matching your search:

Front Genet. 2018 May 7;9:161. doi: 10.3389/fgene.2018.00161. eCollection 2018.

Complex Landscape of Germline Variants in Brazilian Patients With Hereditary and Early Onset Breast Cancer.

Author information

Laboratory of Genomics and Molecular Biology, International Research Center, CIPE/A.C. Camargo Cancer Center, São Paulo, Brazil.
National Institute for Science and Technology in Oncogenomics and Therapeutic Innovation, São Paulo, Brazil.
Laboratory of Bioinformatics and Computational Biology, International Research Center, CIPE/A.C. Camargo Cancer Center, São Paulo, Brazil.
Instituto de Bioinformática e Biotecnologia-2bio, Natal, Brazil.
Instituto Metrópole Digital, Federal University of Rio Grande do Norte, Natal, Brazil.
Bioinformatics Multidisciplinary Environment, Federal University of Rio Grande do Norte, Natal, Brazil.
Research and Development, Fleury Group, São Paulo, Brazil.
Oncogenetics Department, A.C. Camargo Cancer Center, São Paulo, Brazil.
Molecular Oncology Research Center, Barretos Cancer Hospital, São Paulo, Brazil.
Clinical Genetics Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Bethesda, MD, United States.
Brain Institute, Federal University of Rio Grande do Norte, Natal, Brazil.
Barretos School of Health Sciences, Dr. Paulo Prata - FACISB, Barretos, Brazil.


Pathogenic variants in known breast cancer (BC) predisposing genes explain only about 30% of Hereditary Breast Cancer (HBC) cases, whereas the underlying genetic factors for most families remain unknown. Here, we used whole-exome sequencing (WES) to identify genetic variants associated to HBC in 17 patients of Brazil with familial BC and negative for causal variants in major BC risk genes (BRCA1/2, TP53, and CHEK2 c.1100delC). First, we searched for rare variants in 27 known HBC genes and identified two patients harboring truncating pathogenic variants in ATM and BARD1. For the remaining 15 negative patients, we found a substantial vast number of rare genetic variants. Thus, for selecting the most promising variants we used functional-based variant prioritization, followed by NGS validation, analysis in a control group, cosegregation analysis in one family and comparison with previous WES studies, shrinking our list to 23 novel BC candidate genes, which were evaluated in an independent cohort of 42 high-risk BC patients. Rare and possibly damaging variants were identified in 12 candidate genes in this cohort, including variants in DNA repair genes (ERCC1 and SXL4) and other cancer-related genes (NOTCH2, ERBB2, MST1R, and RAF1). Overall, this is the first WES study applied for identifying novel genes associated to HBC in Brazilian patients, in which we provide a set of putative BC predisposing genes. We also underpin the value of using WES for assessing the complex landscape of HBC susceptibility, especially in less characterized populations.


DNA repair genes; cancer predisposition genes; cancer susceptibility; germline pathogenic variants; hereditary breast cancer; whole-exome sequencing

Supplemental Content

Full text links

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