AMPLIFICATION, INCREASED DOSAGE AND IN-SITU EXPRESSION OF THE TELOMERASE RNA GENE IN HUMAN CANCER

Telomere length is maintained by the enzyme, telomerase, which has bee n linked to cellular immortality and tumour progression, However, the reasons for the high levels of telomerase found in human tumours are u nknown, We have mapped the human telomerase RNA gene, (hTR), to chromo some 3q26.3 and show the hTR gene to be amplified in four carcinomas, (2/33 cervix, 1/31 head and neck, 1/9 lung), In addition, increased co py numbers of the hTR locus was also observed in 97% of tumours, By in situ hybridisation, the histological distribution of high levels of h TR expression could be demonstrated in a lung tumour and its metastasi s with hTR amplification, These results are the first report of geneti c alterations involving a known component of telomerase in human cance r, Indeed, it is also the first report of the amplification of a speci fic locus within the chromosome 3q region frequently subject to copy n umber gains in human tumours, In addition, we also show for the first time the histological distribution of the RNA component of telomerase in human tumours.