Gleeson C M, Sloan J M, McGuigan J A, Ritchie A J, Weber J L, Russell S E
Department of Medical Genetics, Queen's University of Belfast, Belfast City Hospital, N. Ireland.
Genes Chromosomes Cancer. 1998 Jan;21(1):49-60.
The development of adenocarcinoma in Barrett's oesophagus is proposed to occur via a stepwise progression recognised histologically as a metaplasia-dysplasia-carcinoma sequence. In order to identify chromosomal loci involved in the malignant transformation of Barrett's epithelium and the development of oesophageal adenocarcinoma, microsatellite analysis was carried out on 17 cases of Barrett's-associated oesophageal adenocarcinoma. Samples of premalignant Barrett's epithelium adjacent to adenocarcinoma were obtained from seven of these cases. Allelic imbalance was detected in > 45% of informative cases of oesophageal adenocarcinoma on chromosome arms 3q (65%), 4q (71%), 5q (59%), 6q (59%), 9p (50%), 9q (47%), 12p (47%), 12q (65%), 17p (76%), and 18q (75%). Allelic imbalance at 4q, 17p, and 18q was significantly higher than the upper 95% confidence interval for background allelic imbalance. Allelic imbalance was detected at several loci in the premalignant epithelium from five of the seven cases studied. These loci included several chromosomal arms that had demonstrated high levels of allelic imbalance in oesophageal adenocarcinoma, namely, 4q (one case), 5q (two cases), 9 (three cases), 12q (five cases), 17p (four cases), and 18q (two cases). Novel microsatellite alleles were detected in both premalignant and malignant Barrett's epithelium. In three cases, dysplastic Barrett's epithelium and adjacent adenocarcinoma demonstrated the same pattern of novel microsatellite alleles at a number of loci. In conclusion, these data indicate chromosomal loci which may be specifically involved in the histological progression of Barrett's epithelium. The detection of shared novel microsatellite alleles in premalignant and malignant Barrett's epithelium is consistent with a process of clonal expansion underlying this progression.
巴雷特食管腺癌的发生被认为是通过一种组织学上可识别的化生-发育异常-癌序列逐步进展的。为了确定参与巴雷特上皮恶性转化和食管腺癌发生的染色体位点，对17例巴雷特相关食管腺癌进行了微卫星分析。其中7例患者获取了与腺癌相邻的癌前巴雷特上皮样本。在食管腺癌信息丰富的病例中，超过45%在染色体臂3q（65%）、4q（71%）、5q（59%）、6q（59%）、9p（50%）、9q（47%）、12p（47%）、12q（65%）、17p（76%）和18q（75%）检测到等位基因失衡。4q、17p和18q的等位基因失衡显著高于背景等位基因失衡的95%置信区间上限。在所研究的7例患者中的5例癌前上皮的几个位点检测到等位基因失衡。这些位点包括在食管腺癌中显示出高等位基因失衡水平的几个染色体臂，即4q（1例）、5q（2例）、9（3例）、12q（5例）、17p（4例）和18q（2例）。在癌前和恶性巴雷特上皮中均检测到新的微卫星等位基因。在3例中，发育异常的巴雷特上皮和相邻腺癌在多个位点显示出相同模式的新微卫星等位基因。总之，这些数据表明了可能特别参与巴雷特上皮组织学进展的染色体位点。在癌前和恶性巴雷特上皮中检测到共享的新微卫星等位基因，这与该进展背后的克隆扩增过程一致。
