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 documento: | Artículo |
| Estado: | Published version |
| Fecha de publicación: | 2016 |
| País: | España |
| Institución: | Universidad de Barcelona |
| Repositorio: | Dipòsit Digital de la UB |
| OAI Identifier: | oai:diposit.ub.edu:2445/118766 |
| Acceso en línea: | https://hdl.handle.net/2445/118766 |
| Nivel de acceso: | Acceso abierto |
| Palabra clave: | Càncer colorectal Factors de risc en les malalties Genètica Malalties hereditàries Colorectal cancer Risk factors in diseases Genetics Genetic diseases |
| _version_ | 1878739499793514496 |
|---|---|
| author | Mur, Pilar |
| author2 | 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 |
| author2_role | author author author author author author author author author author author author author |
| author_browse | Aiza, Gemma Aussó, Susanna Brunet, Joan Capellá, G. (Gabriel) Lázaro García, Conxi Moreno Aguado, Víctor Mur, Pilar Navarro, Matilde Pineda Riu, Marta Puente, Xose S. Sánchez Cuartielles, Elena Urioste, Miguel Valdés Mas, Rafael Valle Velasco, Laura |
| author_facet | 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 |
| author_role | author |
| collection | Dipòsit Digital de la UB |
| description | 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. |
| eu_rights_str_mv | openAccess |
| format | article |
| id | ES_c2adffcaa4e7334cd3848b2fb2cbe549 |
| institution | Universidad de Barcelona |
| instname_str | Universidad de Barcelona |
| network_acronym_str | ES |
| network_name_str | España |
| oai_identifier_str | oai:diposit.ub.edu:2445/118766 |
| publishDate | 2016 |
| publishDateSort | 2016 |
| publisher | Nature Publishing Group |
| publisherStr | Nature Publishing Group |
| reponame_str | Dipòsit Digital de la UB |
| spelling | Scarce evidence of the causal role of germline mutations in UNC5C in hereditary colorectal cancer and polyposis 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 Càncer colorectal Factors de risc en les malalties Genètica Malalties hereditàries Colorectal cancer Risk factors in diseases Genetics Genetic diseases 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. Nature Publishing Group https://hdl.handle.net/2445/118766 |
| spellingShingle | Scarce evidence of the causal role of germline mutations in UNC5C in hereditary colorectal cancer and polyposis Mur, Pilar Càncer colorectal Factors de risc en les malalties Genètica Malalties hereditàries Colorectal cancer Risk factors in diseases Genetics Genetic diseases |
| status_str | publishedVersion |
| title | Scarce evidence of the causal role of germline mutations in UNC5C in hereditary colorectal cancer and polyposis |
| title_full | Scarce evidence of the causal role of germline mutations in UNC5C in hereditary colorectal cancer and polyposis |
| title_fullStr | Scarce evidence of the causal role of germline mutations in UNC5C in hereditary colorectal cancer and polyposis |
| title_full_unstemmed | Scarce evidence of the causal role of germline mutations in UNC5C in hereditary colorectal cancer and polyposis |
| title_short | Scarce evidence of the causal role of germline mutations in UNC5C in hereditary colorectal cancer and polyposis |
| title_sort | Scarce evidence of the causal role of germline mutations in UNC5C in hereditary colorectal cancer and polyposis |
| topic | Càncer colorectal Factors de risc en les malalties Genètica Malalties hereditàries Colorectal cancer Risk factors in diseases Genetics Genetic diseases |
| topic_facet | Càncer colorectal Factors de risc en les malalties Genètica Malalties hereditàries Colorectal cancer Risk factors in diseases Genetics Genetic diseases |
| url | https://hdl.handle.net/2445/118766 |