Frequent detection of aberrant RNA transcripts of the CDKN2 gene in human gastric adenocarcinoma

The tumor-suppressor gene CDKN2 (p16/INK4A/MTSI) is frequently altered in human gastric-cancer cell lines. However, mutation of the CDKN2 gene in primary human gastric-carcinoma tissues as seen through genomic DNA analysis has rarely been reported. In this study, a method combining reverse transcription and nested polymerase chain reaction was developed to detect different RNA transcripts of the CDKN2 gene in human gastric cancers. The results showed that, besides the wild-type CDKN2 transcript, 5 of 11 (45.5%) diffuse-type and 3 of 10 (30%) intestinal-type 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, including 1 case which had an additional inserted sequence from part of CDKN2 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 aberrant CDKN2 RNA transcript. Furthermore, CDKN2 exon 1 or 2 genomic DNA from all the gastric-carcinoma tissues were PCR-amplified and sequenced and no genetic alteration was detected. Therefore, alteration and heterozygous expression of CDKN2 appears to be involved in the pathogenesis of human gastric cancers.