title: Identification of a novel mutation associated with familial adenomatous polyposis and colorectal cancer.
abstract: Colorectal cancer (CRC) is among the most fatal forms of solid tumor in men and women. While the majority of diagnosed CRC cases are sporadic, 15‑25% of patients have a family history of adenomatous polyposis and CRC; however, the associated gene mutations remain largely unidentified. The aim of the present study was to investigate the genomes of a four‑generational Chinese Han family with familial adenomatous polyposis and CRC to identify the potential genetic anomalies associated with the disease. Diagnoses were made by physical and enteroscopic examinations of all the family members. Mutational analyses of the potential CRC‑associated genes were carried out by direct gene sequencing, and the statistically significant differences in polymorphisms between normal and diseased populations were determined. Multiple sequence alignment and protein modeling were conducted using the Vector NTI and DNAMAN software tools. Clinical and pathological features of all the examined patients were consistent with typical familial adenomatous polyposis (FAP) syndrome. From the genomes of these family members, a 131564T>C (p.1125Val>Ala) mutation was identified in exon 15 of the APC gene, and a 1126G>C (p.324Gln>His) mutation was identified in exon 12 of the MUTYH gene. The 131564T>C mutation co‑segregated with the affected individuals in the family and was specifically associated with the incidence of CRC (P=0.018<0.05). The 1125Val residue was highly conserved in the APC protein, and the p.1125Val>Ala mutation led to changes in the secondary structure and hydrophilicity of the APC protein. In conclusion, the APC gene mutation 131564T>C is associated with FAP and the pathogenesis of CRC.
authors.affiliation: Genomics Research Center (One of The State-Province Key Laboratory of Biopharmaceutical Engineering), Harbin Medical University, Harbin 150081, P.R. China.
authors.forename: Fei-Feng
authors.initials: FF
authors.lastname: Li
authors.affiliation: Department of Colorectal Surgery of the Second Affiliated Hospital, Harbin Medical University, Harbin 150086, P.R. China.
authors.forename: Zheng
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Department of Colorectal Surgery of the Second Affiliated Hospital, Harbin Medical University, Harbin 150086, P.R. China.
authors.forename: Peng
authors.initials: P
authors.lastname: Yan
authors.affiliation: Department of Colorectal Surgery of the Second Affiliated Hospital, Harbin Medical University, Harbin 150086, P.R. China.
authors.forename: Xin
authors.initials: X
authors.lastname: Shao
authors.affiliation: Genomics Research Center (One of The State-Province Key Laboratory of Biopharmaceutical Engineering), Harbin Medical University, Harbin 150081, P.R. China.
authors.forename: Xia
authors.initials: X
authors.lastname: Deng
authors.affiliation: HMU-UCFM Centre for Infection and Genomics, Harbin Medical University, Harbin 150081, P.R. China.
authors.forename: Christine
authors.initials: C
authors.lastname: Sam
authors.affiliation: Department of Colorectal Surgery of the Second Affiliated Hospital, Harbin Medical University, Harbin 150086, P.R. China.
authors.forename: Ying-Gang
authors.initials: YG
authors.lastname: Chen
authors.affiliation: Department of Colorectal Surgery of the Second Affiliated Hospital, Harbin Medical University, Harbin 150086, P.R. China.
authors.forename: Yong-Peng
authors.initials: YP
authors.lastname: Xu
authors.affiliation: Department of Colorectal Surgery of the Second Affiliated Hospital, Harbin Medical University, Harbin 150086, P.R. China.
authors.forename: Xi-Shan
authors.initials: XS
authors.lastname: Wang
authors.affiliation: Department of Colorectal Surgery of the Second Affiliated Hospital, Harbin Medical University, Harbin 150086, P.R. China.
authors.forename: Gui-Yu
authors.initials: GY
authors.lastname: Wang
authors.affiliation: Genomics Research Center (One of The State-Province Key Laboratory of Biopharmaceutical Engineering), Harbin Medical University, Harbin 150081, P.R. China.
authors.forename: Shu-Lin
authors.initials: SL
authors.lastname: Liu
mesh_terms: D011125:Adenomatous Polyposis Coli / Q000235:genetics*; D025601:Adenomatous Polyposis Coli Protein / Q000235:genetics*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D019943:Amino Acid Substitution; D000818:Animals; D002648:Child; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense
chemical_list: C555337:APC protein, human; D025601:Adenomatous Polyposis Coli Protein