通过比较基因组杂交分析肠胰系统的散发性神经内分泌肿瘤
Analysis of sporadic neuroendocrine tumours of the enteropancreatic system by comparative genomic hybridisation.
作者信息
Tönnies H, Toliat M R, Ramel C, Pape U F, Neitzel H, Berger W, Wiedenmann B
机构信息
Universitätsklinikum Charité der Humboldt-Universität zu Berlin, Campus Virchow-Klinikum, Institut für Humangenetik, Augustenburger Platz 1, D-13353 Berlin, Germany.
出版信息
Gut. 2001 Apr;48(4):536-41. doi: 10.1136/gut.48.4.536.
BACKGROUND
Chromosomal instability is observed in a wide spectrum of human cancer syndromes. However, to date, little is known of the characteristic genetic changes in sporadic neuroendocrine tumours of the gastroenteropancreatic system.
AIMS AND METHOD
We have studied copy number aberrations (CNAs) in 26 sporadic neuroendocrine tumours of the enteropancreatic system (12 foregut and 14 midgut tumours) by comparative genomic hybridisation (CGH), allowing simultaneous evaluation of the entire tumour genome.
RESULTS
Nearly all tumours (25/26; that is, 96%) showed chromosomal imbalances, including full chromosomal aneuploidies, losses and gains of chromosome arms, interstitial deletions, and amplifications. Whereas gains of chromosomes 4, 5, and 19 were found in both foregut and midgut tumours, gains of chromosomes 20q (58%), 19 (50%), as well as 17p (50%), and partial losses of chromosomes 1p (42%), 2q (42%), 3p, 4q, and 6q (25% each) were frequently observed only in foregut tumours. In contrast, midgut tumours displayed less CNAs. Gains were detected for chromosomes 17q and 19p (57%). Most frequent losses affected chromosomes 18 (43%) and 9p (21%).
CONCLUSIONS
The results of our CGH analyses revealed new distinct candidate regions in the human genome associated with sporadic neuroendocrine tumours. Some of the genetic alterations were shared by foregut and midgut tumours while others discriminated between the two groups. Thus our results allude to the involvement of identical as well as discriminative genetic loci in tumorigenesis and progression of neuroendocrine neoplasms of the foregut and midgut. Based on these findings potential new candidate genes will be discussed.
背景
染色体不稳定在多种人类癌症综合征中均有观察到。然而，迄今为止，对于胃肠胰系统散发性神经内分泌肿瘤的特征性基因变化知之甚少。
目的和方法
我们通过比较基因组杂交（CGH）研究了26例胃肠胰系统散发性神经内分泌肿瘤（12例前肠肿瘤和14例中肠肿瘤）中的拷贝数变异（CNA），从而能够同时评估整个肿瘤基因组。
结果
几乎所有肿瘤（25/26，即96%）均显示出染色体失衡，包括整条染色体的非整倍性、染色体臂的缺失和增加、间质缺失以及扩增。前肠和中肠肿瘤均发现有4号、5号和19号染色体增加，而20q（58%）、19号（50%）以及17p（50%）染色体增加，以及1p（42%）、2q（42%）、3p、4q和6q染色体部分缺失（各25%）仅在前肠肿瘤中频繁观察到。相比之下，中肠肿瘤的CNA较少。检测到17q和19p染色体增加（57%）。最常见的缺失影响18号（43%）和9p（21%）染色体。
结论
我们的CGH分析结果揭示了人类基因组中与散发性神经内分泌肿瘤相关的新的独特候选区域。一些基因改变在前肠和中肠肿瘤中是共有的，而另一些则区分了这两组肿瘤。因此，我们的结果暗示了相同以及有区别的基因位点参与了前肠和中肠神经内分泌肿瘤的发生和进展。基于这些发现，将讨论潜在的新候选基因。
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