The CDKN2A and CDKN2B genes, encoding p16 and p15 respectively, are lo
cated on chromosome 9p21, a locus at which frequent homozygous and het
erozygous deletions occur in many primary human tumors, including esop
hageal carcinoma. CDKN2A and CDKN2B inhibit cyclin dependent kinase 4
(CDK4) and CDK6 and control cellular proliferation by preventing entry
into the S phase of the cell cycle. Their inactivation may contribute
to uncontrolled growth in human cancer. We previously described CDKN2
A exon 2 mutations in a pilot study of 43 esophageal cancers. In order
to determine whether CDKN2A and CDKN2B are frequent targets of 9p21 d
eletion in esophageal carcinogenesis, we have now analyzed 60 primary
esophageal cancers for mutations in both exons 1 and 2 of CDKN2A and C
DKN2B by direct sequencing of PCR amplified genomic DNAs. In conjuncti
on with our previously published data, we have identified a total of e
ight nucleic acid substitutions among 60 esophageal carcinomas; here,
we describe one new CDKN2B nonsense mutation and one new silent CDKN2B
mutation that occurred somatically. Taken together, these results sug
gest that intragenic mutations in CDKN2A and CDKN2B occur in esophagea
l cancer, but that they are infrequent events. In view of the known hi
gh frequency of loss of heterozygosity at the chromosome 9p21 locus in
esophageal cancers, the current data suggest that intragenic mutation
is not the predominant mode of inactivation of CDKN2A and CDKN2B or t
hat other genes are targets of deletion at this locus in these cancers
.