Lovastatin-Induced Sensitization Of Colon Cancer Cells To Apoptosis Is Independent Of Ras And Is Reversed By Geranylgeraniol But Not By Farnesol.

Background.It has been suggested that there are differences in tumorgenesis between sporadic and hereditary nonpolyposis colorectal cancer (HNPCC) associated gastric cancers.The aim of this study was to compare the pattern of DNA copy number changes in these two types of gastric carcinoma.Materials.A total of 25 patients with gastric cancer were included in this study.There were 12 HNPCC patients originating from 12 separate families.A mutated MLH] gene has been detected in 10 families and the remaining two families fulfilled the Amsterdam criteria for HNPCC.The 13 sporadic gastric cancer patients were operated in our department during 1994-1995.The sporadic carcinomas were of intestinal type.A comparative genomic hybridization (CGH) was used to analyze DNA copy number changes of gastric cancer samples.Results.Three (25%) out of the 12 HNPCC samples showed gains of DNA sequences copy numbers affecting 19q, Xp and chromosome 22.Neither high-level amplifications nor losses of DNA copy number were detected.However, 10 (77%) of the 13 sporadic gastric carcinoma samples had multiple DNA copy number changes.The minimal common overlapping regions of the most frequent gains were at 1q22-q31, 8q23-gter, 9q33-gter, 17pl 1.2-q22 and 20q, all at a frequency of 31%.Highlevel amplifications were also seen at 17q21 in three cases (23%).Losses of DNA copy number were rare.Conclusions.Multiple changes in DNA copy numbers seem to have an important role in developing sporadic gastric cancer, whereas gastric cancer in HNPCC may relate to the specific tumorgenesis involving DNA mismatch repair dysfunction.