Multiple types of aberrations in the p16 (INK4a) and the p15(INK4b) genes in 30 esophageal squamous-cell-carcinoma cell lines.

To determine the role and mode of inactivation of thep16andp15genes in human esophageal tumors, we examined alterations and expression of the α and β forms of thep16gene, 5′ CpG island methylation ofp16exon 1α, and alterations of thep15gene in 30 esophageal squamous-cell-carcinoma cell lines. Of 30 such cell lines examined, 28 (93%) showed aberrations of the α form of thep16gene: 18 homozygous deletions, 6 point mutations and 4 hypermethylation. Methylation was exclusively observed in cell lines with the wild-type α form. Of the 6 point mutations, one was observed in exon 1 α, one in the splice acceptor site of intron 1 and the remaining 4 were in exon 2. In the β form, 18 homozygous deletions and 3 point mutations in exon 2 were detected, but no point mutation was found in exon 1 β. All mutations in exon 2 gave rise to premature termination codons in the reading frame of the α transcript, while no non-sense mutations were observed in the reading frame of the β transcript. Among 12 cell lines without homozygous deletions of the α and β forms of thep16gene, the expected wild-type β transcript was observed in 8 cell lines, whereas only one cell line expressed the expected wild-type α transcript. Homozygous deletions of thep15gene were observed in 16 cell lines (53%), and no point mutations were detected. Twelve cell lines had alterations only in the α form of thep16gene, while none showed aberrations exclusively in thep15gene. Taken together, these results indicate that inactivation of the β form of thep16gene and thep15gene are not so frequent as that of the α form of thep16gene in ESC cell lines, suggesting that aberration of the α form ofp16gene is the primary target of 9p loss in ESC.Int. J. Cancer,70:437–442, 1997. © 1997 Wiley-Liss, Inc.