Genomic profiling of gastric cancer predicts lymph node status and survival

被引:89
作者
Weiss, MM
Kuipers, EJ
Postma, C
Snijders, AM
Siccama, I
Pinkel, D
Westerga, J
Meuwissen, SGM
Albertson, DG
Meijer, GA
机构
[1] Vrije Univ Amsterdam, Med Ctr, Dept Pathol, NL-1007 MB Amsterdam, Netherlands
[2] Vrije Univ Amsterdam, Med Ctr, Dept Gastroenterol, NL-1007 MB Amsterdam, Netherlands
[3] Erasmus Univ, Med Ctr, Dept Gastroenterol & Hepatol, Rotterdam, Netherlands
[4] Univ Calif San Francisco, Ctr Canc, San Francisco, CA 94143 USA
[5] KiQ Ltd, Amsterdam, Netherlands
[6] Slotervaart Hosp, Dept Pathol, Amsterdam, Netherlands
关键词
gastric cancer; genomic profiling; survival; microarray CGH;
D O I
10.1038/sj.onc.1206350
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Gastric carcinogenesis is driven by an accumulation of genetic changes that to a large extent occur at the chromosomal level. We analysed the patterns of chromosomal instability in 35 gastric carcinomas and their clinical correlations. With microarray competitive genomic hybridization, genomewide chromosomal copy number changes can be studied with high resolution and sensitivity. A genomewide scanning array with 2275 BAC and PI clones spotted in triplicate was used. This array provided an average resolution of 1.4 Mb across the genome. Patterns of chromosomal aberrations were analysed by hierarchical cluster analysis of the normalized 1092 tumour to normal fluorescence ratios of all clones, and cluster membership was correlated to clinicopathological data including survival. Hierarchical cluster analysis revealed three groups with different genomic profiles that correlated significantly with lymph node status (P = 0.02). Moreover, gastric cancer cases from cluster 3 showed a significantly better prognosis than those from clusters I and 2 (P = 0.02). Genomic profiling of gastric adenocarcinomas based on microarray analysis of chromosomal copy number changes predicted lymph node status and survival. The possibility to discriminate between patients with a high risk of lymph node metastasis could clinically be helpful for selecting patients for extended lymph node resection.
引用
收藏
页码:1872 / 1879
页数:8
相关论文
共 40 条
[1]   Quantitative mapping of amplicon structure by array CGH identifies CYP24 as a candidate oncogene [J].
Albertson, DG ;
Ylstra, B ;
Segraves, R ;
Collins, C ;
Dairkee, SH ;
Kowbel, D ;
Kuo, WL ;
Gray, JW ;
Pinkel, D .
NATURE GENETICS, 2000, 25 (02) :144-146
[2]   Towards a novel classification of human malignancies based on gene expression patterns [J].
Alizadeh, AA ;
Ross, DT ;
Perou, CM ;
van de Rijn, M .
JOURNAL OF PATHOLOGY, 2001, 195 (01) :41-52
[3]  
[Anonymous], HUMAN MOL GENETICS
[4]   Extended lymph-node dissection for gastric cancer [J].
Bonenkamp, JJ ;
Hermans, J ;
Sasako, M ;
van de Velde, CJH .
NEW ENGLAND JOURNAL OF MEDICINE, 1999, 340 (12) :908-914
[5]   Patient survival after D1 and D2 resections for gastric cancer:: long-term results of the MRC randomized surgical trial [J].
Cuschieri, A ;
Weeden, S ;
Fielding, J ;
Bancewicz, J ;
Craven, J ;
Joypaul, V ;
Sydes, M ;
Fayers, P .
BRITISH JOURNAL OF CANCER, 1999, 79 (9-10) :1522-1530
[6]   Cluster analysis and display of genome-wide expression patterns [J].
Eisen, MB ;
Spellman, PT ;
Brown, PO ;
Botstein, D .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1998, 95 (25) :14863-14868
[7]   Helicobacter pylori in gastric cancer established by CagA immunoblot as a marker of past infection [J].
Ekström, AM ;
Held, M ;
Hansson, L ;
Engstrand, L ;
Nyrén, O .
GASTROENTEROLOGY, 2001, 121 (04) :784-791
[8]   Recurrent chromosome changes in 62 primary gastric carcinomas detected by comparative genomic hybridization [J].
Guan, XY ;
Fu, SB ;
Xia, JC ;
Fang, Y ;
Sham, JST ;
Du, BD ;
Zhou, H ;
Lu, S ;
Wang, BQ ;
Lin, YZ ;
Liang, QW ;
Li, XM ;
Du, B ;
Ning, XM ;
Du, JR ;
Li, P ;
Trent, JM .
CANCER GENETICS AND CYTOGENETICS, 2000, 123 (01) :27-34
[9]  
HAUSEN AZ, 2001, GASTROENTEROLOGY, V121, P612
[10]   Colorectal adenoma to carcinoma progression follows multiple pathways of chromosomal instability [J].
Hermsen, M ;
Postma, C ;
Baak, J ;
Weiss, M ;
Rapallo, A ;
Sciutto, A ;
Roemen, G ;
Arends, JW ;
Williams, R ;
Giaretti, W ;
De Goeij, A ;
Meijer, G .
GASTROENTEROLOGY, 2002, 123 (04) :1109-1119