Molecular and functional analysis of chromosome 11 in esophageal carcinomas

Esophageal cancer is an important cancer globally. It ranks eighth in incidence worldwide and seventh locally. Etiological studies have linked many factors to this malignancy. However, the molecular basis of the cancer is poorly understood. Previous studies showed that chromosome 11 is important in esophageal carcinomas. The aims of the present study were to identify possible region(s) containing tumor suppressor gene(s) on chromosome 11 related to esophageal pathogenesis and to investigate its functional role in this cancer. The first aim was achieved by using seventeen polymorphic microsatellite markers spanning the whole chromosome 11 to screen for loss of heterozygosity (LOH) in 38 primary esophageal squamous cell carcinomas. High rates of allelic loss were observed in two chromosomal regions, 11p15.5 and 11q22.3, which had also been reported in other cancers. This suggests the presence of tumor suppressor genes in these areas. The microcell-mediated chromosome transfer technique was used to determine the functional role of chromosome 11 in esophageal carcinogenesis. Chromosome 11 derived from a normal human fibroblast was introduced into the esophageal cancer cell line, T.Tn-6/TSI. Tumorigenic potentials of three chromosome 11-containing microcell hybrids were studied. All the hybrids showed complete suppression of tumorigenicity, including the one that probably received only a 11q fragment. This result indicated that the long arm of chromosome 11 may be sufficient to suppress the tumorigenic phenotype of the esophageal cancer cell line, T.Tn-6/TSI. Overall we demonstrated that chromosome 11 harbors tumor suppressor gene(s), probably localized to the 11q22.3 region, which is/are important for the tumorigenesis of the esophageal cancer