title: GALNT12 is not a major contributor of familial colorectal cancer type X.
abstract: Previous evidence indicates that mutations in the GALNT12 gene might cause a fraction of the unexplained familial colorectal cancer (CRC) cases: GALNT12 is located in 9q22-33, in close proximity to a CRC linkage peak; and germline missense variants that reduce the enzymatic activity of the protein have been identified in CRC patients, some of them with familial CRC history. We hypothesized that mutations in GALNT12 might explain part of the high-risk families grouped as familial CRC type X (fCRC-X), that is, Amsterdam-positive families with mismatch repair proficient tumors. We sequenced the coding regions of the gene in 103 probands of fCRC-X families, finding no functionally relevant mutations. Our results rule out GALNT12 as a major high CRC susceptibility gene. Additional studies are required to provide further evidence about its role as a moderate/low susceptibility gene in familial aggregation of cancer.
authors.affiliation: Hereditary Cancer Program, Catalan Institute of Oncology, IDIBELL, Hospitalet de Llobregat, Spain.
authors.forename: Nuria
authors.initials: N
authors.lastname: Seguí
authors.forename: Marta
authors.initials: M
authors.lastname: Pineda
authors.forename: Matilde
authors.initials: M
authors.lastname: Navarro
authors.forename: Conxi
authors.initials: C
authors.lastname: Lázaro
authors.forename: Joan
authors.initials: J
authors.lastname: Brunet
authors.forename: Mar
authors.initials: M
authors.lastname: Infante
authors.forename: Mercedes
authors.initials: M
authors.lastname: Durán
authors.forename: José Luis
authors.initials: JL
authors.lastname: Soto
authors.forename: Ignacio
authors.initials: I
authors.lastname: Blanco
authors.forename: Gabriel
authors.initials: G
authors.lastname: Capellá
authors.forename: Laura
authors.initials: L
authors.lastname: Valle
mesh_terms: D020413:3' Untranslated Regions; D002899:Chromosomes, Human, Pair 9 / Q000235:genetics; D003123:Colorectal Neoplasms, Hereditary Nonpolyposis / Q000235:genetics* / Q000473:pathology; D053843:DNA Mismatch Repair; D005091:Exons; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D006801:Humans; D020125:Mutation, Missense; D017350:N-Acetylgalactosaminyltransferases / Q000235:genetics* / Q000378:metabolism; D019683:Penetrance; D020641:Polymorphism, Single Nucleotide; D017422:Sequence Analysis, DNA
chemical_list: D020413:3' Untranslated Regions; C465011:GALNT12 protein, human; D017350:N-Acetylgalactosaminyltransferases
keywords: GALNT12; colorectal cancer susceptibility; hereditary colorectal cancer; penetrance