Genetic changes associated with telomerase activity in breast cancer.
Telomerase, the enzyme responsible for maintenance of the telomeres, is absent from the vast majority of somatic cells but is present in most tumours. Little is known about how telomerase is activated in cancer, although it is thought vital for immortalisation to occur. The aim of our study was to identify genetic changes associated with telomerase activity. Thirty-three breast carcinomas were assessed for telomerase activity using the PCR based TRAP assay, and genetic changes by comparative genomic hybridisation (CGH). Seventy-five percent of the tumours were telomerase positive, and these were further divided into low or high level telomerase activity groups. A large number of genetic aberrations were identified but 4 chromosomal regions were identified that correlated with the telomerase status of the tumour. Gain of 1q correlated with telomerase negative tumours, gain of 3q correlated with high level telomerase activity. Gain of 8q correlated with telomerase positive tumours and furthermore with high level telomerase activity; deletion of 17p also correlated with high level telomerase activity. CGH analysis of breast tumours in conjunction with telomerase status has supported early results suggesting the involvement of the telomerase hTR, c-myc and p53 genes in the control of telomerase activity. These genes are located on chromosomes 3q, 8q and 17p. Most importantly, our results have identified the involvement of gene(s) located on chromosome 1q in telomerase expression.
Loveday
R L
RL
Academic Surgical Unit, Castle Hill Hospital, Hull, UK.
Greenman
J
J
Drew
P J
PJ
Monson
J R
JR
Kerin
M J
MJ
D001943:Breast Neoplasms / Q000201:enzymology / Q000235:genetics*; D002869:Chromosome Aberrations; D002898:Chromosomes, Human, Pair 8; D005260:Female; D016259:Genes, myc; D016158:Genes, p53; D006801:Humans; D019098:Telomerase / Q000378:metabolism*
D019098:Telomerase