title: Report of 16 kindreds and one kindred with hMLH1 germline mutation.
abstract: OBJECTIVE
  To analyze the diagnosis and treatment of 16 hereditary nonpolyposis colorectal cancer (HNPCC) kindreds, and to report the first kindred with hMLH1 germline mutation in Mainland China.
  
  
  METHODS
  The diagnosis, treatment and follow-up study of 16 HNPCC kindreds were retrospectively reviewed. Data concerning site of the malignant tumor, age at the diagnosis, history of synchronous and/or metachronous cancer, and histopathology of tumors were recorded. All treatments had won formal consent. PCR and SSCP were used to screen the coding region of hMLH1 and hMSH2 genes. Variant bands were sequenced by a 377 DNA sequencer.
  
  
  RESULTS
  Among sixteen kindreds, sixty-eight patients had a mean age of 50.8 years, including twenty-one multiple cancer patients and forty-six colorectal cancer patients (metachronous colorectal cancers in sixteen). A total of one hundred and one malignant neoplasms were found in these sixty-eight patients, including 50 colonic, 17 rectal, 11 gastric, 7 endometrial, and 4 esophageal cancers. 39.5% colorectal patients had metachronous cancers within ten years who needed reoperations. A germline G265T nonsense mutation was found in the third exon of hMLH1, resulting in a stop codon and truncated protein. Three phenotypically normal family members were also found to carry the mutated gene.
  
  
  CONCLUSIONS
  HNPCC is a typical auto-dominant hereditary disease, the main characteristics include early onset and frequency of cancers; predominance of colorectal, especially right-sided colon cancers; frequency of multiple primary cancers (especially colorectal cancers). Segmental resection for colorectal cancers is not eligible for colorectal cancer patient in HNPCC kindreds. Intensive follow-up is essential for all patients and possible gene carriers. The first HNPCC kindred with hMLH1 gene germline mutation was identified in Mainland China, and three phenotypically normal family members were found to be carriers of the mutated gene. The G265T germline (nonsense) mutation in the third exon of hMLH1 found here had not been reported previously in the literature.
authors.affiliation: Department of Surgery, Peking University First Hospital, No. 8 Xishiku Street, Western Distract, Beijing 100034, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Zhao
authors.forename: Zhen-Jun
authors.initials: ZJ
authors.lastname: Wang
authors.forename: Yu-Feng
authors.initials: YF
authors.lastname: Xu
authors.forename: Yuan-Lian
authors.initials: YL
authors.lastname: Wan
authors.forename: Peng
authors.initials: P
authors.lastname: Li
authors.forename: Yan-Ting
authors.initials: YT
authors.lastname: Huang
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D020137:Base Pair Mismatch; D002352:Carrier Proteins; D002681:China; D003123:Colorectal Neoplasms, Hereditary Nonpolyposis / Q000175:diagnosis / Q000235:genetics*; D004260:DNA Repair; D018095:Germ-Line Mutation; D006801:Humans; D008875:Middle Aged; D000070957:MutL Protein Homolog 1; D009363:Neoplasm Proteins / Q000235:genetics*; D009687:Nuclear Proteins; D010375:Pedigree
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; C501486:MLH1 protein, human; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D000070957:MutL Protein Homolog 1