The TES gene at 7q31.1 is methylated in tumours and encodes a novel growth-suppressing LIM domain protein

Abstract

Many studies suggest that a multi-tissue tumour suppressor gene is located at human chromosome 7q31.1. We have cloned and characterized a novel gene at this locus. The TES gene lies within the minimal region of overlap of several LOH studies and appears to possess the properties of a tumour suppressor. TES is widely expressed and is predicted to encode a protein of 421 amino acids, with three C-terminal LIM domains. Mutation analysis of the coding TES exons in 21 human tumour-derived cell lines revealed the presence of a frameshift mutation in one allele in the breast cancer cell line ZR-75. Methylation of the CpG island at the 5′ end of TES appears to be a remarkably frequent finding, occurring in seven out of 10 ovarian carcinomas and in each of the 30 tumour-derived cell lines tested. Moreover, forced expression of TES in HeLa or OVCAR5 cells, resulted in a profound reduction in growth potential, as determined by the colony formation assay. We believe that TES is a tumour suppressor gene that is inactivated primarily by transcriptional silencing resulting from CpG island methylation.