Scarce evidence of the causal role of germline mutations in UNC5C in hereditary colorectal cancer and polyposis

Germline mutations in UNC5C have been suggested to increase colorectal cancer (CRC) risk, thus causing hereditary CRC. However, the evidence gathered thus far is insufficient to include the study of the UNC5C gene in the routine genetic testing of familial CRC. Here we aim at providing a more conclu...

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Detalhes bibliográficos
Autores: Mur, Pilar, Sánchez Cuartielles, Elena, Aussó, Susanna, Aiza, Gemma, Valdés Mas, Rafael, Pineda Riu, Marta, Navarro, Matilde, Brunet, Joan, Urioste, Miguel, Lázaro García, Conxi, Moreno Aguado, Víctor, Capellá, G. (Gabriel), Puente, Xose S., Valle Velasco, Laura
Formato: artículo
Estado:Versión publicada
Fecha de publicación:2016
País:España
Recursos:Universidad de Barcelona
Repositorio:Dipòsit Digital de la UB
OAI Identifier:oai:diposit.ub.edu:2445/118766
Acesso em linha:https://hdl.handle.net/2445/118766
Access Level:acceso abierto
Palavra-chave:Càncer colorectal
Factors de risc en les malalties
Genètica
Malalties hereditàries
Colorectal cancer
Risk factors in diseases
Genetics
Genetic diseases
Descrição
Resumo:Germline mutations in UNC5C have been suggested to increase colorectal cancer (CRC) risk, thus causing hereditary CRC. However, the evidence gathered thus far is insufficient to include the study of the UNC5C gene in the routine genetic testing of familial CRC. Here we aim at providing a more conclusive answer about the contribution of germline UNC5C mutations to genetically unexplained hereditary CRC and/or polyposis cases. To achieve this goal we sequenced the coding region and exon-intron boundaries of UNC5C in 544 familial CRC or polyposis patients (529 families), using a technique that combines pooled DNA amplification and massively parallel sequencing. A total of eight novel or rare variants, all missense, were identified in eight families. Co-segregation data in the families and association results in case-control series are not consistent with a causal effect for 7 of the 8 identified variants, including c.1882_1883delinsAA (p.A628K), previously described as a disease-causing mutation. One variant, c.2210G > A (p.S737N), remained unclassified. In conclusion, our results suggest that the contribution of germline mutations in UNC5C to hereditary colorectal cancer and to polyposis cases is negligible.

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