hTR repressor-related gene on human chromosome 10p15.1

Summary Somatic cells express genes that suppress telomerase activity and these genes may be inactivated in tumour cells. We postulatedthat cancer cells acquire immortality by activation of telomerase by the loss of such a gene. We have reported recently that a telomeraserepressor gene may be located on 10p15.1 by deletion mapping using microcell-mediated chromosome transfer (MMCT), radiated microcellfusion (RMF), fluorescent in situ hybridization (FISH) and STS analysis. To independently confirm this result, we correlated ex pression of RNAcomponent of telomerase (hTR) as a marker of telomerase expression by in situ hybridization with allelic loss in pulmonary carc inoid tumours.Unlike most malignant tumours, pulmonary carcinoids (which are low-grade malignant tumours) are heterogeneous for telomeraseexpression. Loss of 5 closely spaced polymorphic markers on 10p15.1, especially D10S1728, were highly correlated with hTR expre ssion. Inan additional experiment, 10p15.1 showed higher and more significant correlation than any region of 3p where it has been predicted asanother chromosomal location of telomerase repressor with allelic loss of the region. Our findings strongly suggest that 10p15.1 harbours agene involved in repression of telomerase RNA component in human somatic cells and each putative repressor (on 3p and 10p) may actindependently. © 2001 Cancer Research Campaign http://www.bjcancer.com Keywords: hTR; in situ hybridization; mapping; chromosome 10p15; telomerase repressor gene; loss of heterozygosity 1510