title: Analysis of Small Fragment Deletions of the APC gene in Chinese Patients with Familial Adenomatous Polyposis, a Precancerous Condition.
abstract: BACKGROUND
  Familial adenomatous polyposis (FAP) is an autosomal dominant inherited disease mainly caused by mutations of the adenomatous polyposis coli (APC) gene with almost complete penetrance. These colorectal polyps are precancerous lesions that will inevitable develop into colorectal cancer at the median age of 40-year old if total proctocolectomy is not performed. So identification of APC germline mutations has great implications for genetic counseling and management of FAP patients. In this study, we screened APC germline mutations in Chinese FAP patients, in order to find novel mutations and the APC gene germline mutation characteristics of Chinese FAP patients.
  
  
  METHODS
  The FAP patients were diagnosed by clinical manifestations, family histories, endoscope and biopsy. Then patients peripheral blood samples were collected, afterwards, genomic DNA was extracted. The mutation analysis of the APC gene was conducted by direct polymerase chain reaction (PCR) sequencing for micromutations and multiplex ligation-dependent probe amplification (MLPA) for large duplications and/or deletions.
  
  
  RESULTS
  We found 6 micromutations out of 14 FAP pedigrees, while there were no large duplications and/or deletions found. These germline mutations are c.5432C>T(p. Ser1811Leu), two c.3926_3930delAAAAG (p.Glu1309AspfsX4), c.3921_3924delAAAA (p.Ile1307MetfsX13), c3184_3187delCAAA(p.Gln1061AspfsX59) and c4127_4126delAT (p.Tyr1376LysfsX9), respectively, and all deletion mutations resulted in a premature stop codon. At the same time, we found c.3921_3924delAAAA and two c.3926_3930delAAAAG are located in AAAAG short tandem repeats, c3184_3187delCAAA is located in the CAAA interrupted direct repeats, and c4127_4128 del AT is located in the 5'-CCTGAACA-3' ,3'-ACAAGTCC-5 palindromes (inverted repeats) of the APC gene. Furthermore, deletion mutations are mostly located at condon 1309.
  
  
  CONCLUSIONS
  Though there were no novel mutations found as the pathogenic gene of FAP in this study, we found nucleotide sequence containing short tandem repeats and palindromes (inverted repeats), especially the 5 bp base deletion at codon 1309, are mutations in high incidence area in APC gene.
authors.affiliation: Department of Medical Oncology, Jiangsu Cancer Hospital affiliated to Nanjing Medical University, Nanjing, Jiangsu, P.R. China E-mail : J Feng: fjif@medmail.com.cn; S. Chen: chensenqing2008@126.com.
authors.forename: Qing-Wei
authors.initials: QW
authors.lastname: Chen
authors.forename: Xiao-Mei
authors.initials: XM
authors.lastname: Zhang
authors.forename: Jian-Nong
authors.initials: JN
authors.lastname: Zhou
authors.forename: Xin
authors.initials: X
authors.lastname: Zhou
authors.forename: Guo-Jian
authors.initials: GJ
authors.lastname: Ma
authors.forename: Ming
authors.initials: M
authors.lastname: Zhu
authors.forename: Yuan-Ying
authors.initials: YY
authors.lastname: Zhang
authors.forename: Jun
authors.initials: J
authors.lastname: Yu
authors.forename: Ji-Feng
authors.initials: JF
authors.lastname: Feng
authors.forename: Sen-Qing
authors.initials: SQ
authors.lastname: Chen
mesh_terms: D011125:Adenomatous Polyposis Coli / Q000235:genetics*; D000328:Adult; D044466:Asian People / Q000235:genetics*; D001483:Base Sequence; D018389:Codon, Nonsense / Q000235:genetics; D015179:Colorectal Neoplasms / Q000235:genetics; D004252:DNA Mutational Analysis / Q000379:methods; D005260:Female; D017353:Gene Deletion; D017491:Genes, APC / Q000502:physiology*; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D018095:Germ-Line Mutation / Q000235:genetics; D006801:Humans; D008297:Male; D018895:Microsatellite Repeats / Q000235:genetics; D008875:Middle Aged; D010375:Pedigree; D011230:Precancerous Conditions / Q000235:genetics*; D017384:Sequence Deletion / Q000235:genetics*
chemical_list: D018389:Codon, Nonsense