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

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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Main Authors: Mur, Pilar, Elena, Sánchez-Cuartielles, Aussó, Susanna, Aiza, Gemma, Rafael, Valdés-Mas, Pineda, Marta, Navarro, Matilde, Brunet, Joan, Urioste, Miguel, Lázaro, Conxi, Moreno, Victor, Capellá, Gabriel, Puente, Xose S., Valle, Laura
Format: Online
Language:English
Published: Nature Publishing Group 2016
Online Access:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4745060/
id pubmed-4745060
recordtype oai_dc
spelling pubmed-47450602016-02-16 Scarce evidence of the causal role of germline mutations in UNC5C in hereditary colorectal cancer and polyposis Mur, Pilar Elena, Sánchez-Cuartielles Aussó, Susanna Aiza, Gemma Rafael, Valdés-Mas Pineda, Marta Navarro, Matilde Brunet, Joan Urioste, Miguel Lázaro, Conxi Moreno, Victor Capellá, Gabriel Puente, Xose S. Valle, Laura Article 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 2016-02-08 /pmc/articles/PMC4745060/ /pubmed/26852919 http://dx.doi.org/10.1038/srep20697 Text en Copyright © 2016, Macmillan Publishers Limited http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
repository_type Open Access Journal
institution_category Foreign Institution
institution US National Center for Biotechnology Information
building NCBI PubMed
collection Online Access
language English
format Online
author Mur, Pilar
Elena, Sánchez-Cuartielles
Aussó, Susanna
Aiza, Gemma
Rafael, Valdés-Mas
Pineda, Marta
Navarro, Matilde
Brunet, Joan
Urioste, Miguel
Lázaro, Conxi
Moreno, Victor
Capellá, Gabriel
Puente, Xose S.
Valle, Laura
spellingShingle Mur, Pilar
Elena, Sánchez-Cuartielles
Aussó, Susanna
Aiza, Gemma
Rafael, Valdés-Mas
Pineda, Marta
Navarro, Matilde
Brunet, Joan
Urioste, Miguel
Lázaro, Conxi
Moreno, Victor
Capellá, Gabriel
Puente, Xose S.
Valle, Laura
Scarce evidence of the causal role of germline mutations in UNC5C in hereditary colorectal cancer and polyposis
author_facet Mur, Pilar
Elena, Sánchez-Cuartielles
Aussó, Susanna
Aiza, Gemma
Rafael, Valdés-Mas
Pineda, Marta
Navarro, Matilde
Brunet, Joan
Urioste, Miguel
Lázaro, Conxi
Moreno, Victor
Capellá, Gabriel
Puente, Xose S.
Valle, Laura
author_sort Mur, Pilar
title 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_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_sort scarce evidence of the causal role of germline mutations in unc5c in hereditary colorectal cancer and polyposis
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.
publisher Nature Publishing Group
publishDate 2016
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4745060/
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