Gastric cancers in young and elderly patients show different genomic profiles
Gastric cancers in young and elderly patients show different genomic profiles
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DOI：
10.1002/path.2085
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发表时间：
2007-01-01
影响因子：
7.3
通讯作者：
Meijer, G. A.
中科院分区：
文献类型：
--
作者：
Buffart, T. E.;Carvalho, B.;Meijer, G. A.
虽然大多数胃癌发生在老年患者中，但这种常见疾病的大量病例发生在年轻患者中。胃癌在基因组水平上是一种异质性疾病，不同模式的DNA拷贝数改变与不同的临床行为相关。本研究的目的是探讨DNA拷贝数改变与胃癌发病年龄的关系。采用5000个BAC克隆阵列，采用全基因组微阵列比较基因组杂交（array CGH）技术，对17例年龄小于50岁（中位43（21-49）岁）和29例年龄大于或等于70岁（中位75（70-83）岁）患者的46份石蜡包埋胃癌组织样本进行DNA分离分析。利用TMEV软件对肿瘤与正常参考荧光信号强度的1092比进行模式归一化和平滑处理，通过分层聚类分析分析DNA拷贝数畸变的模式，然后将聚类隶属度与年龄组相关。此外，使用CGH Multi-array进行监督分析。阵列CGH数据的分层聚类分析显示，三个不同基因组谱的聚类与年龄显著相关（p = 0.006）。聚类1以年轻患者为主，老年患者分为聚类2和聚类3。染色体区域11q23.3和19p13.3对肿瘤谱的年龄相关差异贡献最大。青年和老年胃癌患者属于不同基因组图谱的群体，这可能反映了不同的发病机制。版权所有(c) 2006大不列颠和爱尔兰病理学会。约翰·威利父子有限公司出版。
Although most gastric cancers occur in elderly patients, a substantial number of cases of this common disease occur in young patients. Gastric cancer is a heterogeneous disease at the genomic level and different patterns of DNA copy number alterations are associated with different clinical behaviour. The aim of the present study was to explore differences in DNA copy number alterations in relation to age of onset of gastric cancer. DNA isolated from 46 paraffin-embedded gastric cancer tissue samples from 17 patients less than 50 years of age [median 43 (21-49) years] and 29 patients greater than or equal to 70 years of age [median 75 (70-83) years] was analysed by genome-wide microarray comparative genomic hybridization (array CGH) using an array of 5000 BAC clones. Patterns of DNA copy number aberrations were analysed by hierarchical cluster analysis of the mode-normalized and smoothed 1092 ratios of tumour to normal reference fluorescence signal intensities using TMEV software, after which cluster membership was correlated with age group. In addition, supervised analysis was performed using CGH Multi-array. Hierarchical cluster analysis of the array CGH data revealed three clusters with different genomic profiles that correlated significantly with age (p = 0.006). Cluster 1 mainly contained young patients, while elderly patients were divided over clusters 2 and 3. Chromosome regions 11q23.3 and 19p13.3 contributed most to age-related differences in tumour profiles. Gastric cancers of young and old patients belong to groups with different genomic profiles, which likely reflect different pathogenic mechanisms of the disease. Copyright (c) 2006 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.