Gastric cancers in young and elderly patients show different genomic profiles

被引:52
作者
Buffart, T. E.
Carvalho, B.
Hopmans, E.
Brehm, V.
Kranenbarg, E. Klein
Schaaiji-Visser, T. B. M.
Eijk, P. P.
van Grieken, N. C. T.
Ylstra, B.
van de Velde, C. J. H.
Meijer, G. A.
机构
[1] Vrije Univ Amsterdam, Med Ctr, Dept Pathol, NL-1007 MB Amsterdam, Netherlands
[2] Leiden Univ, Med Ctr, Dept Surg, Leiden, Netherlands
关键词
gastric cancer; array CGH; genomic profiling; age;
D O I
10.1002/path.2085
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
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.
引用
收藏
页码:45 / 51
页数:7
相关论文
共 41 条
[31]   Gastric adenocarcinoma in patients 40 years of age or younger [J].
Theuer, CP ;
deVirgilio, C ;
Keese, G ;
French, S ;
Arnell, T ;
Tolmos, J ;
Klein, S ;
Powers, W ;
Oh, T ;
Stabile, BE .
AMERICAN JOURNAL OF SURGERY, 1996, 172 (05) :473-477
[32]  
Theuer CP, 1998, CANCER-AM CANCER SOC, V83, P25, DOI 10.1002/(SICI)1097-0142(19980701)83:1<25::AID-CNCR4>3.0.CO
[33]  
2-D
[34]  
Tsukamoto Y, 1998, LAB INVEST, V78, P699
[35]   CGHMultiArray:: exact P-values for multi-array comparative genomic hybridization data [J].
van de Wiel, MA ;
Smeets, SJ ;
Brakenhoff, RH ;
Ylstra, B .
BIOINFORMATICS, 2005, 21 (14) :3193-3194
[36]   DNA copy number changes in young gastric cancer patients with special reference to chromosome 19 [J].
Varis, A ;
van Rees, B ;
Weterman, M ;
Ristimäki, A ;
Offerhaus, J ;
Knuutila, S .
BRITISH JOURNAL OF CANCER, 2003, 88 (12) :1914-1919
[37]  
Weiss MM, 1999, J CLIN PATHOL-MOL PA, V52, P243
[38]  
Weiss MM, 2004, CELL ONCOL, V26, P307
[39]   Genomic profiling of gastric cancer predicts lymph node status and survival [J].
Weiss, MM ;
Kuipers, EJ ;
Postma, C ;
Snijders, AM ;
Siccama, I ;
Pinkel, D ;
Westerga, J ;
Meuwissen, SGM ;
Albertson, DG ;
Meijer, GA .
ONCOGENE, 2003, 22 (12) :1872-1879
[40]  
Xie SH, 1997, CANCER RES, V57, P2295