BRCA2 gene: a candidate for clinical testing in familial colorectal cancer type X

Autor:	P, Garre, L, Martín, J, Sanz, A, Romero, A, Tosar, I, Bando, P, Llovet, P, Diaque, B, García-Paredes, E, Díaz-Rubio, M, de la Hoya, T, Caldés
Rok vydání:	2014
Předmět:	Adult BRCA2 Protein Male Genotype Loss of Heterozygosity Middle Aged Colorectal Neoplasms Hereditary Nonpolyposis Polymorphism Single Nucleotide Pedigree Mutation Humans Family Female Genetic Predisposition to Disease Genetic Testing Alleles Genetic Association Studies Germ-Line Mutation Aged
Zdroj:	Clinical genetics. 87(6)
ISSN:	1399-0004
Popis:	Familial colorectal cancer type X (FCCX) encompasses a group of families with dominant inheritance pattern of colorectal cancer (CRC) but no alteration in any known CRC susceptibility gene. Therefore, the explanation of their susceptibility is a priority to offer an accurate genetic counseling. We screened the 27 coding exons and exon-intron boundaries of BRCA2 in 48 FCCX probands. We identified 29 variants including a frameshift mutation. Deleterious variant c.3847_3848delGT p.(Val1283Lysfs*2) showed cosegregation with disease as well as loss of heterozygosity (LOH) in CRC tumor DNA. This is the first evidence of germline BRCA2 pathogenic mutation associated with CRC risk. Furthermore, missense variants c.502CA p.(Pro168Thr), c.5744CT p.(Thr1915Met) and c.7759CT p.(Leu2587Phe) were proposed as candidate risk alleles based on cosegregation, LOH tumor analysis and in silico testing.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=pmid________::0d7fb70bd3097bd3c5b6e20f4e177551 https://pubmed.ncbi.nlm.nih.gov/24814045 Zobrazit plný text záznamu Plný text