title: A de novo germline mutation of APC for inheritable colon cancer in a Chinese family using multigene next generation sequencing.
abstract: Inheritable colorectal cancers (CRC) accounted for about 20% of the CRC cases, such as hereditary nonpolyposis colorectal cancer (HNPCC), Gardner syndrome and familial adenomatous polyposis (FAP). A four-generation Han Chinese family was found affected with polyposis in colons. Inferred from the pedigree structure, the disease in this family showed an autosomal dominant inheritance model. To locate the causal mutations in this family, genomic DNAs were extracted and the next generation sequencing for 5 genes relating to colon cancer performed by Ion Torrent Personal Genome Machine with a 314 chip. The reads were aligned with human reference genome hg19 to call variants in the 5 genes. After analysis, 14 variants were detected in the sequenced sample and 13 been collected in dbSNP database and assigned with a rs identification number. In these variants, 9 were synonymous, 4 missense and 1 non-sense. In them, 2 rare variants (c.694C>T in APC and c.1690A>G in MSH2) might be the putative causal mutations for familial adenomatous polyposis (FAP) since the rarity of the mutated allele in normal controls. c.694C>T was detected in only affected members and generated a premature stop codon in APC. It should be a de novo germline mutation making APC containing this stop codon as targets for nonsense-mediated mRNA decay (NMD). c.1690A>G in MSH2 was not only detected in affected members, but also in normal ones in the family. Functional prediction revealed that the amino acid affected by this variant had no effect on the function of MSH2. Here, we report a de novo germline mutation of APC as the causal variant in a Chinese family with inheritable colon cancer by the next generation sequencing.
authors.affiliation: Department of Gynaecology and Obstetrics, Second Hospital of Jinlin University, Changchun 130041, PR China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Beijing DnaLead Science and Technology Co., LTD, Beijing 102600, PR China. Electronic address: guantlv@126.com.
authors.forename: Guanting
authors.initials: G
authors.lastname: Lu
authors.affiliation: Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing 100101, PR China; University of Chinese Academy of Sciences, Beijing 100049, PR China.
authors.forename: Qingtao
authors.initials: Q
authors.lastname: Hu
authors.affiliation: Beijing DnaLead Science and Technology Co., LTD, Beijing 102600, PR China.
authors.forename: Xueyan
authors.initials: X
authors.lastname: Wang
authors.affiliation: Beijing DnaLead Science and Technology Co., LTD, Beijing 102600, PR China.
authors.forename: Chaohua
authors.initials: C
authors.lastname: Li
authors.affiliation: Beijing DnaLead Science and Technology Co., LTD, Beijing 102600, PR China.
authors.forename: Yuegan
authors.initials: Y
authors.lastname: Mao
authors.affiliation: Department of Gynaecology and Obstetrics, Second Hospital of Jinlin University, Changchun 130041, PR China. Electronic address: cuimanhua@126.com.
authors.forename: Manhua
authors.initials: M
authors.lastname: Cui
mesh_terms: D025601:Adenomatous Polyposis Coli Protein / Q000235:genetics*; D044466:Asian People / Q000235:genetics; D002681:China; D015179:Colorectal Neoplasms / Q000235:genetics*; D004252:DNA Mutational Analysis / Q000379:methods; D020022:Genetic Predisposition to Disease; D018095:Germ-Line Mutation; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D008297:Male; D010375:Pedigree
chemical_list: D025601:Adenomatous Polyposis Coli Protein
keywords: Inheritable colon cancer; Premature stop codon; de novo germline mutation