MOLECULAR-GENETIC PROFILES OF COLITIS-ASSOCIATED NEOPLASMS
MOLECULAR-GENETIC PROFILES OF COLITIS-ASSOCIATED NEOPLASMS
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DOI：
10.1016/0016-5085(94)90167-8
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发表时间：
1994-08-01
期刊：
影响因子：
29.4
通讯作者：
KINZLER, KW
中科院分区：
文献类型：
--
作者：
KERN, SE;REDSTON, M;KINZLER, KW
背景/目的：慢性特发性结肠炎患者的主要长期风险是发生结直肠发育不良和腺癌。这些病变中是否存在特定的遗传变化将为结肠炎相关的发育不良与癌症发展的关系提供重要的见解。方法：采用病例研究方法，对6例溃疡性结肠炎或克罗恩结肠炎患者的晚期发育不良和癌进行详细的分子遗传分析。结果：在每一种发育不良和癌中都发现了大量的遗传改变。这些基因改变涉及许多在散发性结直肠肿瘤中发现的相同靶点，包括多个等位基因缺失、微卫星不稳定性以及K-ras、p53和APC基因的突变。发育不良向癌的进展通常伴随着这些突变的积累。结论：基因改变在结肠炎相关瘤变中很常见，就像散发性结直肠瘤变一样。这可能对结肠炎患者的评估和治疗具有重要意义。
Background/Aims:A major long-term risk for patients with chronic idiopathic colitis is the development of colorectal dysplasia and adenocarcinoma. The presence or absence of specific genetic changes in these lesions will provide important insights into the relationship of colitis-associated dysplasia and the development of carcinoma.Methods:A case-study approach was used to develop detailed molecular genetic profiles of advanced dysplasias and carcinomas from six patients with ulcerative colitis or Crohn's colitis.Results:Numerous genetic alterations were identified in each of the dysplasias and carcinomas profiled. These genetic alterations involved many of the same targets found in sporadic colorectal tumors and included multiple sites of allelic deletion, microsatellite instabilities, and mutations of the K-ras,p53, and APC genes. The progression of dysplasia to carcinoma was often accompanied by an accumulation of these mutations.Conclusions:Genetic alterations are common in colitis-associated neoplasia, just as in sporadic colorectal neoplasia. This could have important implications for the evaluation and treatment of patients with colitis.