Willenbucher R F, Zelman S J, Ferrell L D, Moore D H, Waldman F M
Cancer Center, University of California, San Francisco, USA.
Gastroenterology. 1997 Sep;113(3):791-801. doi: 10.1016/s0016-5085(97)70173-2.
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.
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.
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.
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.
在溃疡性结肠炎（UC）相关肿瘤进展过程中，基因组紊乱是否先于发育异常的组织学发展尚不清楚。本研究的主要目的是确定染色体改变是否在UC相关肿瘤形成的进展途径中早期出现。
使用一组着丝粒周围探针，对5例UC相关癌结肠切除标本中癌灶、发育异常灶及UC累及的非发育异常上皮部位解离的细胞核进行荧光原位杂交（FISH）。采用比较基因组杂交（CGH）检测从这些部位提取的DNA中的克隆性染色体缺失和增加。
FISH分析显示，与对照组相比，所有癌、发育异常及非发育异常的UC累及上皮活检标本的染色体拷贝数均有显著且通常较为明显的改变。除1个发育异常和癌的分析部位外，在所有部位以及5个非发育异常部位中的2个部位，CGH检测到了克隆性染色体缺失和增加。FISH和CGH经常检测到18号染色体的相对缺失。
染色体改变可能在UC相关肿瘤进展的早期出现，且似乎先于发育异常的组织学发展。18q的相对缺失可能在UC相关肿瘤形成的进展中起重要作用。将染色体改变的检测作为一个中间终点，可能有助于识别患结直肠癌风险较高的患者。
