6th ESACP Congress, Heidelberg, April 7-11, 1999

A146
COMPARATIVE GENOMIC HYBRIDIZATION REVEALS A CONSISTENT PATTERN OF CHROMOSOMAL ABERRATIONS IN GASTRIC ADENOCARCINOMAS.
Van Grieken NCT, Weiss MM, Hermsen M, Meijer GA, Craanen ME, Bloemena E, Baak JPA, Meuwissen SGM, Kuipers EJ

Depts. of Gastroenterology and Pathology, Free University Hospital, Amsterdam, Dept. of Pathology Free University Hospital Amsterdam, Netherlands

Gastric carcinogenesis is strongly associated with H.pylori (Hp) infection. However, the exact mechanisms by which Hp induces gastric cancer are unknown. The aim of the present study was to explore chromosomal aberrations in adenocarcinomas of the stomach by comparative genomic hybridization (CGH). This technique allows the screening for chromosomal gains and losses in the tumour genome. Forty six patients (35 were male, 11 were female, age 27-85 yrs) were investigated. Tumour DNA was extracted from formaldehyde-fixed paraffin-embedded material after microdissection. CGH data were correlated to clinico-pathological variables and to the results of DNA flow cytometry. Each tumour was found to contain at least six chromosomal aberrations. Chromosomes 8q+, 12q-, 13q+, 17p-, 19p-, 19q- and 22q- were most frequently involved (24%, 43%, 26%, 50%, 33%, 39% and 37%, respectively). Gains at chromosome 8 contained the c-MYC locus at 8q24. Losses of 17p correspond to loss of p53 tumour suppressor function. For gains of 13q, no clear candidate oncogene has yet been identified. Twenty cases out of 39 tested were DNA diploid and nineteen were DNA aneuploid by DNA flow cytometry. As expected, higher DNA indices correlated with more chromosomal gains and less losses. Conclusion: Comparative genomic hybridization shows consistent non-random chromosomal aberrations in gastric cancer. This allows a more detailed genetic analysis of presursor lesions which may yield a more precise chronology of events in (H. pylori-associated) gastric cancer. Disclosure: This study was funded by Glaxo Wellcome bv, the Netherlands.