FREQUENT DETECTION OF ABERRANT RNA TRANSCRIPTS OF THE CDKN2 GENE IN HUMAN GASTRIC ADENOCARCINOMA

The tumor-suppressor gene CDKN2 (p16/IK4A/MTS1) is frequently altered in human gastric-cancer cell lines. However, mutation of the CDKN2 gen e in primary human gastric-carcinoma tissues as seen through genomic D NA analysis has rarely been reported. In this study, a method combinin g reverse transcription and nested polymerase chain reaction was devel oped to detect different RNA transcripts of the CDKN2 gene in human ga stric cancers. The results showed that, besides the wild-type CDKN2 tr anscript, 5 of 11 (45.5%) diffuse-type and 3 of 10 (30%) intestinal-ty pe primary gastric adenocarcinoma had aberrant CDKN2 RNA transcripts. Among these 8 tumorous specimens with abnormal CDKN2 RNA transcripts, 6 had intragenic deletions of part of both CDKN2 exons 1 and 2, includ ing 1 case which had an additional inserted sequence from part of CDKN 2 intron 2. In addition, 1 case had a deletion of part of CDKN2 exon 1 and 1 case had its entire exon 2 deleted. In contrast, matched normal gastric mucosal tissues from the same patients did not have any aberr ant CDKN2 RNA transcript. Furthermore, CDKN2 exon 1 or 2 genomic DNA f rom all the gastric-carcinoma tissues were PCR-amplified and sequenced and no genetic alteration was detected. Therefore, alteration and het erozygous expression of CDKN2 appears to be involved in the pathogenes is of human gastric cancers. (C) 1997 Wiley-Liss, Inc.