Association of K-ras mutations with p16 methylation in human colon cancer

摘要: Abstract Background & Aims: K- ras mutations are early genetic changes in colon cancer. p16, a tumor-suppressor gene, is inactivated neoplasms by mutation, deletion, or methylation. The aims of this study were to determine p16 methylation status and its possible association with human Methods: DNA isolated from 8 cancer cell lines 41 microdissected tissue samples was analyzed. determined using two analytical methods. level expression reverse-transcription polymerase chain reaction Northern blot. sequence analysis. methyltransferase activity microassay. Parental –transformed IEC-18 cells used the potential between Results: Methylated found 100% lines, 55% cancers, 54% adenomas, 25% transitional mucosa but not normal colonic epithelium. Forty-five percent cancers 38% adenomas showed both Of 11 10 specimens methylated p16. In contrast, 13 wild-type ras, only 3 ( P = 0.001). Stable transformation increased activity, suppressed Treatment inhibitor (azadeoxycytidine) resulted reexpression cells, suggesting that Conclusions: occurs frequently closely associated mutations. GASTROENTEROLOGY 1999;116:1063-1071