Adenomatous polyposis coli gene mutations in ulcerative colitis-associated dysplasias and cancers versus sporadic colon neoplasms.
Adenomatous polyposis coli gene mutations in ulcerative colitis-associated dysplasias and cancers versus sporadic colon neoplasms.
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发表时间：
1995-05
期刊：
影响因子：
11.2
通讯作者：
L. Tarmin;Jing Yin;N. Harpaz;M. Kozam;Jeroen Noordzij;Lilian B. Antonio;H. Jiang;O. Chan;K. Cymes;S. Meltzer
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作者：
L. Tarmin;Jing Yin;N. Harpaz;M. Kozam;Jeroen Noordzij;Lilian B. Antonio;H. Jiang;O. Chan;K. Cymes;S. Meltzer
大肠腺瘤性息肉病（APC）基因突变发生在大多数散发性结肠腺瘤和癌。溃疡性结肠炎（UC）相关结肠癌的前体病变，虽然在形态上类似于散发性腺瘤，但在生物学上可能与它们不同，实际上，管理不同。由于散发性腺瘤也可能发生在UC中，因此区分这些形式的瘤形成的方法可能具有临床实用性。我们检查了33例UC相关发育不良和癌症患者以及23例散发性结肠肿瘤患者的APC突变。密码子686-1693，含有64%的所有报告的APC突变（突变簇区域），使用体外合成蛋白质测定筛选截短突变。33例UC相关异型增生和癌症患者中有2例（6%）共有3个截短型APC突变，均发生在坦率癌中，而23例散发性结肠肿瘤患者中有17例（74%）有突变。DNA测序证实了密码子1460中的两个突变，用终止密码子替换精氨酸，以及一个2碱基对缺失，导致密码子1477处的移码和终止。一个样本含有这些APC突变中的每一个。APC突变簇区域突变率的明显差异与将散发性结肠肿瘤与UC相关发育不良和癌症分开的其他生物学特征一致。这些数据提高了非腺瘤性UC发育不良可能由不同于散发性结肠癌发生的分子途径引起的可能性，并且他们建议通过分子测定来区分UC中发生的散发性腺瘤和发育不良。
Adenomatous polyposis coli (APC) gene mutations occur in most sporadic colonic adenomas and carcinomas. Precursor lesions of ulcerative colitis (UC)-associated colon carcinomas, although morphologically similar to sporadic adenomas, may be biologically distinct from them and are, in fact, managed differently. Since sporadic adenomas may also occur in UC, a method of discriminating between these forms of neoplasia could have clinical utility. We examined 33 patients with UC-associated dysplasias and cancers and 23 sporadic colon neoplasms in a side-by-side comparison for APC mutations. Codons 686-1693, containing 64% of all reported APC mutations (the mutation cluster region), were screened for truncating mutations using an in vitro synthesized protein assay. Two of thirty-three patients (6%) with UC-associated dysplasias and cancers had a total of three truncating APC mutations, all in frank carcinomas, while 17 of 23 (74%) with sporadic colonic neoplasms had mutations. DNA sequencing confirmed two mutations in codon 1460, replacing arginine with a stop codon, as well as one 2-base pair deletion, resulting in a frameshift and a stop at codon 1477. One specimen contained one each of these APC mutations. This apparent contrast in mutation rates at the mutation cluster region of APC is consistent with other biological characteristics separating sporadic colon neoplasms from UC-associated dysplasias and cancers. These data raise the possibility that nonadenomatous UC dysplasias may arise by a molecular pathway distinct from that prevailing in sporadic colon carcinogenesis, and they suggest a molecular assay to discriminate between sporadic adenomas and dysplasias occurring in UC.