ABSTRACT: Purpose: To improve clinical outcome of gastric cancer patients, most emphasis is on improving therapeutic regimens, including more extensive surgery as well as (neo)adjuvant chemotherapy. The present study set out to identify, based on DNA copy number profiling, subgroups of patients with different clinical outcomes who thus would qualify for different therapy intensities. Experimental Design: DNA of 206 gastric cancer patients was isolated and analyzed by genome wide array comparative genomic hybridization. DNA copy number profiles were evaluated and correlated to lymph node status and survival. In addition, HSP90 protein expression was analyzed and correlated to survival in 290 gastric cancer patients. Results: Frequent (>20%) DNA copy number gains were observed on chromosomes 1p, 6p, 7p, 7q, 8q, 11q, 12q, 13q, 16p, 16q, 17q, 19p, 19q, 20p, 20q, 21q and 22q, and losses on chromosomes 4p, 4q, 6p, 6q, 9p, 13q and 21q. Lymph node negative gastric cancers showed significantly more losses on chromosomes 5q11.2-q35.1, 10q11.23-21.3 and 14q32.11-q32.33. In addition, losses on 5q11.2-q31.3 and 14q32.11-q32.33 were highly correlated to good clinical outcome, in both lymph node negative and positive gastric cancer patients. Loss of expression of HSP90, located on chromosome 14q32.2, correlated to good survival time. Conclusion: Genome wide DNA copy number profiling allows to identify a subgroup of gastric cancers, marked by losses on chromosomes 5q11.2-q31.3 and 14q32.11-q32.33 that have an excellent clinical outcome after surgery alone, and patients with these tumors are unlikely to benefit from additional intensified therapies. Possible biological mechanisms could involve loss of heat shock proteins, of which the coding genes are located at these chromosomal regions.
