title: Scarce evidence of the causal role of germline mutations in UNC5C in hereditary colorectal cancer and polyposis.
abstract: 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.
authors: Hereditary Cancer Program, Catalan Institute of Oncology, IDIBELL, 08908 Hospitalet de Llobregat, Spain.
authors: Pilar
authors: P
authors: Mur
authors: Hereditary Cancer Program, Catalan Institute of Oncology, IDIBELL, 08908 Hospitalet de Llobregat, Spain.
authors: Elena
authors: E
authors: Sánchez-Cuartielles
authors: Unit of Biomarkers and Susceptibility, Cancer Prevention and Control Program, Catalan Institute of Oncology, IDIBELL and CIBERESP, 08908 Hospitalet de Llobregat, Spain.
authors: Susanna
authors: S
authors: Aussó
authors: Hereditary Cancer Program, Catalan Institute of Oncology, IDIBELL, 08908 Hospitalet de Llobregat, Spain.
authors: Gemma
authors: G
authors: Aiza
authors: Department of Biochemistry and Molecular Biology, Instituto Universitario de Oncología del Principado de Asturias, Universidad de Oviedo, 33006 Oviedo, Spain.
authors: Rafael
authors: R
authors: Valdés-Mas
authors: Hereditary Cancer Program, Catalan Institute of Oncology, IDIBELL, 08908 Hospitalet de Llobregat, Spain.
authors: Marta
authors: M
authors: Pineda
authors: Hereditary Cancer Program, Catalan Institute of Oncology, IDIBELL, 08908 Hospitalet de Llobregat, Spain.
authors: Matilde
authors: M
authors: Navarro
authors: Hereditary Cancer Program, Catalan Institute of Oncology, IDIBGi, 17007 Girona, Spain.|Department of Medical Sciences, School of Medicine, University of Girona, 17071 Girona, Spain.
authors: Joan
authors: J
authors: Brunet
authors: Familial Cancer Clinical Unit, Human Cancer Genetics Program, Spanish National Cancer Research Centre (CNIO) and Center for Biomedical Network Research on Rare Diseases (CIBERER), 28029 Madrid, Spain.
authors: Miguel
authors: M
authors: Urioste
authors: Hereditary Cancer Program, Catalan Institute of Oncology, IDIBELL, 08908 Hospitalet de Llobregat, Spain.
authors: Conxi
authors: C
authors: Lázaro
authors: Unit of Biomarkers and Susceptibility, Cancer Prevention and Control Program, Catalan Institute of Oncology, IDIBELL and CIBERESP, 08908 Hospitalet de Llobregat, Spain.|Department of Clinical Sciences, School of Medicine, University of Barcelona, 08907 Hospitalet de Llobregat, Spain.
authors: Victor
authors: V
authors: Moreno
authors: Hereditary Cancer Program, Catalan Institute of Oncology, IDIBELL, 08908 Hospitalet de Llobregat, Spain.
authors: Gabriel
authors: G
authors: Capellá
authors: Department of Biochemistry and Molecular Biology, Instituto Universitario de Oncología del Principado de Asturias, Universidad de Oviedo, 33006 Oviedo, Spain.
authors: Xose S
authors: XS
authors: Puente
authors: Hereditary Cancer Program, Catalan Institute of Oncology, IDIBELL, 08908 Hospitalet de Llobregat, Spain.
authors: Laura
authors: L
authors: Valle
mesh_terms: D011125:Adenomatous Polyposis Coli / Q000235:genetics* / Q000473:pathology; D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D002478:Cells, Cultured; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000473:pathology; D004247:DNA / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D019175:DNA Methylation; D005091:Exons; D005260:Female; D018095:Germ-Line Mutation; D006801:Humans; D019656:Loss of Heterozygosity / Q000235:genetics; D008214:Lymphocytes / Q000166:cytology / Q000378:metabolism; D008297:Male; D018895:Microsatellite Repeats; D008875:Middle Aged; D020125:Mutation, Missense; D000075386:Netrin Receptors; D010375:Pedigree; D016133:Polymerase Chain Reaction; D011401:Promoter Regions, Genetic; D012326:RNA Splicing; D011956:Receptors, Cell Surface / Q000235:genetics*; D017422:Sequence Analysis, DNA
chemical_list: D000075386:Netrin Receptors; D011956:Receptors, Cell Surface; C115727:UNC5C protein, human; D004247:DNA