摘要
AIM: To analyze the diagnosis and treatment of 16 hereditarynonpolyposis colorectal cancer (HNPCC) kindreds, and toreport the first kindred with hMLH1 germline mutation inChina's Mainland.METHODS: The diagnosis, treatment and follow-up study of16 HNPCC kindreds were retrospectively reviewed. Dataconceming site of the malignant tumor, age st the diagnosis,history of synchronous and/ or metachronous cancer, andhistopathology of tumors were recorded. All treatments hadwon formal consent. PCR and SSCP were used to screen thecoding region of hMLH1 and hMSH2 genes. Variant bandswere sequenced by a 377 DNA sequencer.RESULTS: Among sixteen kindreds, sixty-eight patients hada mean age of 50.8 years, including twenty-one multiplecancer patients and forty-six colorectal cancer patients(metachronous colorectal cancers in sixteen). A total of onehundred and one malignant neoplasms were found in thesesixty-eight patients, including 50 colonic, 17 rectal, 11gastric, 7 endometrial, and 4 esophageal cancers. 39.5%colorectal patients had metachronous cancers within tenyears who needed reopeertions. A germline G265T nonsensemutation was found in the third exon of hMLH1, resulting in astop codon and truncated protein. Three phenotypically normalfamily members were also found to carry the mutated gene.ONCLUSION: HNPCC is a typical auto-dominant hereditaryisease, the main characteristics include early onset andfrequency of cancers; predominance of colorectal,especially right-sided colon cancers; frequency of multipleprimary cancers (especially colorectal cancers). Segmentalresection for colorectal cancers is not eligible for colorectalcancer patient in HNPCC kindreds. Intensive follow-up isessential for all patients and possible gene carriers. The firstHNPCC kindred with hMUH1 gene germline mutation wasidentified in China's Mainland, and three phenotypicallynormal family members were found to be carriers of themutated gene. The G265T germline (nonsense) mutation inthe third exon of hMLH1 found here had not been reportedpreviously in the literature.
AIM: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 China's Mainland. 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 hMLHI,resulting in a stop codon and truncated protein.Three phenotypically normal family members were also found to carry the mutated gene.CONCLUSION: 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 hMLHl gene germline mutation was identified in China's Mainland, 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 hMLHl found here had not been reported previously in the literature.
基金
National Natural Science Foundation of China,No,39970817
a Fund from National Education Committee (1999)
