title: Genomic profiling of gastric cancer predicts lymph node status and survival.
abstract: 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 P1 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 log(2) 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 1 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.
authors.affiliation: Department of Gastroenterology, VU University Medical Centre, Amsterdam, The Netherlands.
authors.forename: Marjan M
authors.initials: MM
authors.lastname: Weiss
authors.forename: Ernst J
authors.initials: EJ
authors.lastname: Kuipers
authors.forename: Cindy
authors.initials: C
authors.lastname: Postma
authors.forename: Antoine M
authors.initials: AM
authors.lastname: Snijders
authors.forename: Ivar
authors.initials: I
authors.lastname: Siccama
authors.forename: Daniel
authors.initials: D
authors.lastname: Pinkel
authors.forename: Johan
authors.initials: J
authors.lastname: Westerga
authors.forename: Stefan G M
authors.initials: SG
authors.lastname: Meuwissen
authors.forename: Donna G
authors.initials: DG
authors.lastname: Albertson
authors.forename: Gerrit A
authors.initials: GA
authors.lastname: Meijer
mesh_terms: D000818:Animals; D008207:Lymphatic Metastasis; D009693:Nucleic Acid Hybridization; D020411:Oligonucleotide Array Sequence Analysis; D011379:Prognosis; D013274:Stomach Neoplasms / Q000235:genetics* / Q000473:pathology; D016019:Survival Analysis