p53 point mutations in dysplastic and cancerous ulcerative colitis lesions.
p53 point mutations in dysplastic and cancerous ulcerative colitis lesions.
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DOI：
10.1016/0016-5085(93)90639-t
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发表时间：
1993-06
期刊：
影响因子：
29.4
通讯作者：
Jing Yin;N. Harpaz;Y. Tong;Ying Huang;Jacqueline N. Laurin;B. Greenwald;M. Hontanosas;C. Newkirk;S. Meltzer
中科院分区：
文献类型：
--
作者：
Jing Yin;N. Harpaz;Y. Tong;Ying Huang;Jacqueline N. Laurin;B. Greenwald;M. Hontanosas;C. Newkirk;S. Meltzer
背景：溃疡性结肠炎引起的结直肠异型增生和癌的分子基础知之甚少。肿瘤抑制基因p53的杂合性丢失常发生在肿瘤性溃疡性结肠炎病变中。影响p53的点突变与其他癌症中的杂合性丢失相关。方法：对45例溃疡性结肠炎相关异型增生和癌患者进行单链构象多态性分析、DNA测序和杂合性丢失研究。结果：20例患者的26个病变中检测到p53点突变，其中癌18个，异型增生相关肿块6个，扁平异型增生1个，淋巴结转移1个。在两个案例中，相同的p53突变，观察癌和相邻的异型增生。观察到导致氨基酸取代的错义突变以及导致过早终止密码子的无义突变。串联突变，其中一个以上的序列改变发生在同一等位基因的p53，也被检测到。点突变伴随着其他p53等位基因在10例患者中的8个信息的杂合性丢失和突变assess.Conclusions：这些研究结果表明，失活的p53突变和杂合性丢失是一种常见的机制，在溃疡性结肠炎的恶性转化。这也意味着，与散发性结直肠癌不同，溃疡性结肠炎相关的肿瘤进展可能在相对早期的非侵袭性阶段涉及p53失活。
Background:The molecular basis of colorectal dysplasia and carcinoma arising in ulcerative colitis is poorly understood. Loss of heterozygosity involving the tumor suppressor gene p53 occurs frequently in neoplastic ulcerative colitis lesions. Point mutation affecting p53 is associated with loss of heterozygosity in other cancers. Therefore, it was determined whether p53 point mutation occurs in ulcerative colitis-associated neoplasia.Methods:Single-strand conformation polymorphism analysis, DNA sequencing, and loss of heterozygosity studies were performed on 45 patients with ulcerative colitis-associated dysplasia and carcinoma.Results:Point mutations were detected in 26 lesions from 20 patients, including 18 carcinomas, 6 dysplasia-associated masses, 1 flat dysplasia, and 1 lymph node metastasis. In two cases, identical p53 mutations were observed in both carcinoma and adjacent dysplasia. Missense mutations causing amino acid substitutions as well as nonsense mutations resulting in premature stop codons were seen. Tandem mutations, in which more than 1 sequence alteration occurred on the same allele of p53, were also detected. Point mutation was accompanied by loss of the other p53 allele in 8 of 10 patients informative for both loss of heterozygosity and mutation assays.Conclusions:These findings suggest that inactivation of p53 by mutation and loss of heterozygosity is a common mechanism of malignant transformation in ulcerative colitis. They also imply that in contrast to sporadic colorectal carcinoma, ulcerative colitis-associated neoplastic progression may involve p53 inactivation at relatively earlynoninvasive stages.