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 been linked to cellular immortality and tumour progression. However, the reasons for the high levels of telomerase found in human tumours are unknown. We have mapped the human telomerase RNA gene, (hTR), to chromosome 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 copy numbers of the hTR locus was also observed in 97% of tumours. By in situ hybridisation, the histological distribution of high levels of hTR expression could be demonstrated in a lung tumour and its metastasis with hTR amplification. These results are the first report of genetic alterations involving a known component of telomerase in human cancer. Indeed, it is also the first report of the amplification of a specific locus within the chromosome 3q region frequently subject to copy number 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.
Soder
A I
AI
CRC Department of Medical Oncology, University of Glasgow, Bearsden, UK.
Hoare
S F
SF
Muir
S
S
Going
J J
JJ
Parkinson
E K
EK
Keith
W N
WN
D002277:Carcinoma / Q000235:genetics*; D002874:Chromosome Mapping; D002893:Chromosomes, Human, Pair 3; D005260:Female; D005784:Gene Amplification; D006258:Head and Neck Neoplasms / Q000235:genetics; D006801:Humans; D017403:In Situ Hybridization; D008175:Lung Neoplasms / Q000235:genetics; D012334:RNA, Neoplasm / Q000032:analysis; D019098:Telomerase / Q000032:analysis / Q000235:genetics*; D014018:Tissue Distribution; D002583:Uterine Cervical Neoplasms / Q000235:genetics
D012334:RNA, Neoplasm; D019098:Telomerase