title: Correlation between genomic alterations assessed by array comparative genomic hybridization, prognostically informative histologic subtype, stage, and patient survival in gastric cancer.
abstract: It is difficult to evaluate the prognostic value of histologic criteria in gastric cancer because of the high variability of morphologic patterns. Recently, histologic subtypes of low, intermediate, or high malignant potential have been identified, providing the basis for a prognostically informative grading system. Because array comparative genomic hybridization systems allow systematic analysis of chromosome alterations, which may be prognostically and pathogenetically informative, we applied high-resolution genome-wide array comparative genomic hybridization to archival material from 81 gastric cancer cases followed for a median of 150 months after surgery. The DNA extracted from paraffin sections gave useful results in 49 tumors, 18 of which were of low-grade, 24 of intermediate, and 7 of high-grade histotypes. Based on the number of chromosome aberrations and the presence/absence of amplifications, 3 tumor clusters of increasing genomic lesion severity were constructed, which proved to correlate significantly with histologic grade and stage as well as with patient survival. Further investigation documented the lower number and severity of genomic alterations in tumors with microsatellite DNA instability and high CD8-rich lymphoid response; the close association of 8p23.1 amplification with cardial cancer; the frequent amplification of genes involved in cell renewal (CDC6, HER2, GRB7, IGFBP4) at 17q12-q21.1, with close histochemical correlation with HER2 membranous expression; and more sporadic amplification of chromosome regions harboring important oncogenes like MYC, KRAS, NRAS, CRKL, CCNE1, or ZNF217. We conclude that genome-wide array comparative genomic hybridization of gastric cancer contributes prognostically relevant information providing a genetic background for histologic grading.
authors.affiliation: Biology and Medical Genetics, University of Pavia, 27100 Pavia, Italy.
authors.forename: Elena
authors.initials: E
authors.lastname: Rossi
authors.forename: Catherine
authors.initials: C
authors.lastname: Klersy
authors.forename: Rachele
authors.initials: R
authors.lastname: Manca
authors.forename: Orsetta
authors.initials: O
authors.lastname: Zuffardi
authors.forename: Enrico
authors.initials: E
authors.lastname: Solcia
mesh_terms: D002869:Chromosome Aberrations; D016000:Cluster Analysis; D055028:Comparative Genomic Hybridization / Q000379:methods*; D004273:DNA, Neoplasm / Q000235:genetics; D015894:Genome, Human / Q000235:genetics*; D023281:Genomics; D006801:Humans; D053208:Kaplan-Meier Estimate; D053842:Microsatellite Instability; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D009857:Oncogenes / Q000235:genetics; D016612:Paraffin Embedding; D011379:Prognosis; D013274:Stomach Neoplasms / Q000235:genetics* / Q000401:mortality; D016019:Survival Analysis
chemical_list: D004273:DNA, Neoplasm