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...
| Autores: | , , , , , , , , , , , , , |
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| Tipo de recurso: | artículo |
| Fecha de publicación: | 2016 |
| País: | España |
| Institución: | Instituto de Salud Carlos III (ISCIII) |
| Repositorio: | Repisalud |
| Idioma: | inglés |
| OAI Identifier: | oai:repisalud.isciii.es:20.500.12105/8869 |
| Acceso en línea: | http://hdl.handle.net/20.500.12105/8869 |
| Access Level: | acceso abierto |
| Palabra clave: | Adenomatous Polyposis Coli Adult Aged Case-Control Studies Cells, Cultured Colorectal Neoplasms DNA DNA Methylation Exons Female Germ-Line Mutation Humans Loss of Heterozygosity Lymphocytes Male Microsatellite Repeats Middle Aged Mutation, Missense Netrin Receptors Pedigree Polymerase Chain Reaction Promoter Regions, Genetic RNA Splicing Receptors, Cell Surface Sequence Analysis, DNA |
| Sumario: | 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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