Frequent Somatic Mutation of the MTS1/CDK4I (Multiple Tumor Suppressor/Cyclin-dependent Kinase 4 Inhibitor) Gene in Esophageal Squamous Cell Carcinoma

We previously reported frequent loss of heterozygosity on chromosome 9p in esophageal carcinomas and suggested that a tumor suppressor gene located on this chromosomal arm might be involved in development of these cancers. Since recently published studies have shown that a gene mapped on chromosome 9p21, MTS1/CDK4I (multiple tumor suppressor 1/cyclin-dependent kinase 4 inhibitor), is frequently mutated in various types of tumors, we chose to examine esophageal squamous cell carcinomas for mutations in this candidate gene. DNA sequence analyses revealed somatic mutations of MTSHCDK4I in 14 of 27 tumors examined; 8 were frame-shift mutations and 6 were missense mutations. These results suggested that the MTSHCDK4I gene is a tumor suppressor the inactivation of which plays an important role during carcinogenesis of the squamous cell type of esophageal carcinoma.