Your browser doesn't support javascript.
loading
Using Co-segregation and Loss of Heterozygosity Analysis to Define the Pathogenicity of Unclassified Variants in Hereditary Breast Cancer Patients.
Grasel, Rebeca Silveira; Felicio, Paula Silva; de Paula, André Escremim; Campacci, Natalia; Garcia, Felipe Antônio de Oliveira; de Andrade, Edilene Santos; Evangelista, Adriane Feijó; Fernandes, Gabriela Carvalho; Sabato, Cristina da Silva; De Marchi, Pedro; Souza, Cristiano de Pádua; de Paula, Cláudia Alessandra Andrade; Torrezan, Giovana Tardin; Galvão, Henrique de Campos Reis; Carraro, Dirce Maria; Palmero, Edenir Inêz.
Afiliación
  • Grasel RS; Molecular Oncology Research Center, Barretos Cancer Hospital, São Paulo, Brazil.
  • Felicio PS; Molecular Oncology Research Center, Barretos Cancer Hospital, São Paulo, Brazil.
  • de Paula AE; Center of Molecular Diagnosis, Barretos Cancer Hospital, São Paulo, Brazil.
  • Campacci N; Molecular Oncology Research Center, Barretos Cancer Hospital, São Paulo, Brazil.
  • Garcia FAO; Molecular Oncology Research Center, Barretos Cancer Hospital, São Paulo, Brazil.
  • de Andrade ES; Molecular Oncology Research Center, Barretos Cancer Hospital, São Paulo, Brazil.
  • Evangelista AF; Molecular Oncology Research Center, Barretos Cancer Hospital, São Paulo, Brazil.
  • Fernandes GC; Center of Molecular Diagnosis, Barretos Cancer Hospital, São Paulo, Brazil.
  • Sabato CDS; Center of Molecular Diagnosis, Barretos Cancer Hospital, São Paulo, Brazil.
  • De Marchi P; Department of Medical Oncology, Barretos Cancer Hospital, São Paulo, Brazil.
  • Souza CP; Oncoclinicas, Rio de Janeiro, Brazil.
  • de Paula CAA; Department of Medical Oncology, Barretos Cancer Hospital, São Paulo, Brazil.
  • Torrezan GT; Department of Oncogenetics, Barretos Cancer Hospital, São Paulo, Brazil.
  • Galvão HCR; Genomic Diagnostic Center, AC Camargo Cancer Center, São Paulo, Brazil.
  • Carraro DM; Genomics and Molecular Biology Group, CIPE - A. C. Camargo Cancer Center, São Paulo, Brazil.
  • Palmero EI; Department of Oncogenetics, Barretos Cancer Hospital, São Paulo, Brazil.
Front Oncol ; 10: 571330, 2020.
Article en En | MEDLINE | ID: mdl-33134171
The use of gene panels introduces a new dilemma in the genetics field due to the high frequency of variants of uncertain significance (VUS). The objective of this study was to provide evidence that may help in the classification of these germline variants in terms of their clinical impact and association with the disease in question. A total of 52 unrelated women at-risk for HBOC and negative for BRCA1/BRCA2 pathogenic variants were evaluated through a gene panel comprising 14 breast and/or ovarian cancer susceptibility genes. Of the 453 germline variants identified, 15 variants (classes 3, 4, and 5) in the ATM, BRIP1, CHEK2, MRE11A, MUTHY, PALB2, RAD50, and RAD51C genes were evaluated via databases, co-segregation studies and loss of heterozygosity in the tumor. The co-segregation analysis allowed the establishment of an association with the presence of variants and the risk of cancer for variant c.316C>T in the BRIP1 gene. Four variants of uncertain significance showed loss of heterozygosity in the tumor (ATM c.4709T>C; CHEK2 c.1036C>T; PALB2 c.1001A>G, and RAD50 c.281T>C), which is an indication of pathogenicity. Thus, the present study provides novel evidence that favors the association of variants in moderate-risk genes with the development of hereditary breast cancer.
Palabras clave
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: Front Oncol Año: 2020 Tipo del documento: Article País de afiliación: Brasil Pais de publicación: Suiza
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: Front Oncol Año: 2020 Tipo del documento: Article País de afiliación: Brasil Pais de publicación: Suiza