Characterization of the D184Y variant in the BRIP1 gene in a family with breast an...
| Full text | |
| Author(s): Show less - |
Torrezan, Giovana T.
[1, 2]
;
de Almeida, Fernanda G. dos Santos R.
[1]
;
Figueiredo, Marcia C. P.
[1]
;
de Figueiredo Barros, Bruna D.
[1]
;
de Paula, Claudia A. A.
[1]
;
Valieris, Renan
[3]
;
de Souza, Jorge E. S.
[4, 5, 6]
;
Ramalho, Rodrigo F.
[1]
;
da Silva, Felipe C. C.
[1]
;
Ferreira, Elisa N.
[7, 1]
;
de Nobrega, Amanda F.
[8]
;
Felicio, Paula S.
[9]
;
Achatz, Maria I.
[8, 10]
;
de Souza, Sandro J.
[11, 2, 6]
;
Palmero, Edenir I.
[9, 12]
;
Carraro, Dirce M.
[1, 2]
Total Authors: 16
|
| Affiliation: Show less - | [1] CIPE AC Camargo Canc Ctr, Int Res Ctr, Lab Genom & Mol Biol, Sao Paulo - Brazil
[2] Natl Inst Sci & Technol Oncogen & Therapeut Innov, Sao Paulo - Brazil
[3] CIPE AC Camargo Canc Ctr, Int Res Ctr, Lab Bioinformat & Computat Biol, Sao Paulo - Brazil
[4] Inst Bioinformat & Biotecnol 2Bio, Natal, RN - Brazil
[5] Univ Fed Rio Grande do Norte, Inst Metropole Digital, Natal, RN - Brazil
[6] Univ Fed Rio Grande do Norte, Bioinformat Multidisciplinary Environm, Natal, RN - Brazil
[7] Fleury Grp, Res & Dev, Sao Paulo - Brazil
[8] AC Camargo Canc Ctr, Oncogenet Dept, Sao Paulo - Brazil
[9] Barretos Canc Hosp, Mol Oncol Res Ctr, Sao Paulo - Brazil
[10] NCI, Clin Genet Branch, Div Canc Epidemiol & Genet, NIH, US Dept HHS, Bethesda, MD 20892 - USA
[11] Univ Fed Rio Grande do Norte, Brain Inst, Natal, RN - Brazil
[12] Dr Paulo Prata FACISB, Barretos Sch Hlth Sci, Barretos - Brazil
Total Affiliations: 12
|
| Document type: | Journal article |
| Source: | FRONTIERS IN GENETICS; v. 9, MAY 7 2018. |
| Web of Science Citations: | 4 |
| Abstract | |
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. (AU) | |
| FAPESP's process: | 13/24633-2 - Molecular characterization of at high risk families for hereditary breast cancer, negatives for BRCA1/BRCA2: looking for the BRCAx |
| Grantee: | Edenir Inêz Palmero |
| Support type: | Regular Research Grants |
| FAPESP's process: | 08/57887-9 - National Institute of Oncogenomics |
| Grantee: | Luiz Paulo Kowalski |
| Support type: | Research Projects - Thematic Grants |
| FAPESP's process: | 13/23277-8 - Molecular aspects involved in the development and progression of breast ductal carcinoma: investigation of carcinoma in situ progression and the role of BRCA1 mutation in the triple negative tumor |
| Grantee: | Dirce Maria Carraro |
| Support type: | Research Projects - Thematic Grants |