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. 2009 Sep;455(3):213-23.
doi: 10.1007/s00428-009-0814-y. Epub 2009 Aug 21.

High resolution analysis of DNA copy-number aberrations of chromosomes 8, 13, and 20 in gastric cancers

Tineke E Buffart  1 , Nicole C T van Grieken, Marianne Tijssen, Jordy Coffa, Bauke Ylstra, Heike I Grabsch, Cornelis J H van de Velde, Beatriz Carvalho, Gerrit A Meijer
Affiliations

High resolution analysis of DNA copy-number aberrations of chromosomes 8, 13, and 20 in gastric cancers

Tineke E Buffart et al. Virchows Arch. 2009 Sep.

Abstract

DNA copy-number gains of chromosomes 8q, 13q, and 20q are frequently observed in gastric cancers. Moreover gain of chromosome 20q has been associated with lymph node metastasis. The aim of this study was to correlate DNA copy-number changes of individual genes on chromosomes 8q, 13q, and 20q in gastric adenocarcinomas to clinicopathological data. DNA isolated from 63 formalin-fixed and paraffin-embedded gastric adenocarcinoma tissue samples was analyzed by whole-genome microarray comparative genomic hybridization and by multiplex ligation-dependent probe amplification (MLPA), targeting 58 individual genes on chromosomes 8, 13, and 20. Using array comparative genomic hybridization, gains on 8q, 13q, and 20q were observed in 49 (77.8%), 25 (39.7%), and 49 (77.8%) gastric adenocarcinomas, respectively. Gain of chromosome 20q was significantly correlated with lymph node metastases (p = 0.05) and histological type (p = 0.02). MLPA revealed several genes to be frequently gained in DNA copy number. The oncogene c-myc on 8q was gained in 73% of the cancers, while FOXO1A and ATP7B on 13q were both gained in 28.6% of the cases. Multiple genes on chromosome 20q showed gains in more than 60% of the cancers. DNA copy-number gains of TNFRSF6B (20q13.3) and ZNF217 (20q13.2) were significantly associated with lymph node metastasis (p = 0.02) and histological type (p = 0.02), respectively. In summary, gains of chromosomes 8q, 13q, and 20q in gastric adenocarcinomas harbor DNA copy-number gains of known and putative oncogenes. ZNF217 and TNFRSF6B are associated with important clinicopathological variables, including lymph node status.

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Figures

Fig. 1
Fig. 1
Heatmap of DNA copy number ratios of 11 genes on chromosome 8, 12 genes on chromosome 13, and 35 genes on chromosome 20. The columns represent different gastric adenocarcinomas, and the rows represent the different genes. Darker squares indicate higher DNA copy number ratios
Fig. 2
Fig. 2
Box plot of DNA copy number ratios of the gene TNFRFS6B between lymph node-negative and lymph node-positive gastric adenocarcinomas. Lymph node-positive gastric adenocarcinomas have significantly higher DNA copy number ratios of TNFRFS6B compared with lymph node-negative gastric adenocarcinomas (p = 0.02). The central box covers the middle 50% of the data values between the upper and lower quartiles. The line across the box indicates the median. The whiskers extend from the box to the minimum and maximum values with the exception of outliers, which are marked by circles
Fig. 3
Fig. 3
Box plot of DNA copy number ratios of the gene ZNF217 between intestinal-, diffuse-, and mixed-type gastric adenocarcinomas. DNA copy number ratios of ZNF217 are significantly different between gastric adenocarcinomas of different histological types (p = 0.02)
Fig. 4
Fig. 4
Scatter plots of the log2 ratios of the BAC clone and MLPA probe of the TNFRFS6B (a) and ZNF217 (b) genes. A significant correlation was detected for both genes (p < 0.001, r = 0.57 and r = 0.51, respectively)
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