Chromosomal alterations in ulcerative colitis-related neoplastic progression
Chromosomal alterations in ulcerative colitis-related neoplastic progression
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DOI：
10.1016/s0016-5085(97)70173-2
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发表时间：
1997-09-01
期刊：
影响因子：
29.4
通讯作者：
Waldman, FM
中科院分区：
文献类型：
--
作者：
Willenbucher, RF;Zelman, SJ;Waldman, FM
背景和目标：目前尚不清楚基因组紊乱是否先于溃疡性结肠炎（UC）相关肿瘤进展中发育不良的组织学发展。本研究的主要目的是确定染色体改变是否发生在UC相关肿瘤进展途径的早期。研究方法：荧光原位杂交（FISH）进行核解离的癌症，异型增生和UC相关的非异型增生上皮在5个UC相关的癌症结肠切除术标本的癌症，异型增生的网站上使用一个面板的pericentromeric探针。比较基因组杂交（CGH）被用来检测克隆染色体的损失和增益从这些网站提取的DNA。结果如下：FISH分析显示，与对照组相比，所有癌症、异型增生和非异型增生UC相关上皮的活检标本的染色体拷贝数发生了显著且经常是戏剧性的变化。CGH检测到克隆性染色体丢失和获得，但在所有的异型增生和癌症的分析网站，并在五个非异型增生网站的两个。FISH和CGH常检测到18号染色体的相对丢失。结论：染色体改变可能发生在UC相关肿瘤进展的早期，似乎先于发育不良的组织学发展。18q的相对丢失在UC相关肿瘤的进展中可能是重要的。检测染色体变异作为中间终点可能被证明是有用的，在确定患者的发展为结直肠癌的高风险。
Background & Aims: It is unclear whether genomic derangement precedes the histological development of dysplasia in ulcerative colitis (UC)-related neoplastic progression. The primary aim of this study was to determine if chromosomal alterations occur early in the progression pathway of UC-related neoplasia. Methods: Fluorescence in situ hybridization (FISH) was performed on nuclei dissociated from sites of cancer, dysplasia, and UC-involved nondysplastic epithelium in five UC-related cancer colectomy specimens using a panel of pericentromeric probes. Comparative genomic hybridization (CGH) was used to detect clonal chromosomal losses and gains in DNA extracted from these sites. Results: FISH analysis revealed significant and often dramatic alterations in chromosome copy number compared with controls in all biopsy specimens of cancer, dysplasia, and nondysplastic UC-involved epithelium. Clonal chromosomal losses and gains were detected by CGH in all but one analyzed site of dysplasia and cancer and in two of the five nondysplastic sites. FISH and CGH frequently detected the relative loss of chromosome 18. Conclusions: Chromosomal alterations may occur early in UC-related neoplastic progression and seem to precede the histological development of dysplasia. Relative loss of 18q may be important in the progression of UC-related neoplasia. The detection of chromosomal alterations as an intermediate end point may prove useful in identifying patients at high risk for the development of colorectal cancer.