Telomere reduction in human colorectal carcinoma and with ageing.
We have hypothesized that end-to-end chromosome fusions observed in some tumours could play a part in genetic instability associated with tumorigenesis and that fusion may result from the loss of the long stretches of G-rich repeats found at the ends of all linear chromosomes. We therefore asked whether there is telomere loss or reduction in common tumours. Here we show that in most of the colorectal carcinomas that we analysed, there is a reduction in the length of telomere repeat arrays relative to the normal colonic mucosa from the same patient. We speculate on the consequences of this loss for tumorigenesis. We also show that the telomere arrays are much smaller in colonic mucosa and blood than in fetal tissue and sperm, and that there is a reduction in average telomere length with age in blood and colon mucosa. We propose that the telomerase is inactive in somatic tissues, and that telomere length is an indicator of the number of cell divisions that it has taken to form a particular tissue and possibly to generate tumours.
Hastie
N D
ND
MRC Human Genetics Unit, Western General Hospital, Edinburgh, UK.
Dempster
M
M
Dunlop
M G
MG
Thompson
A M
AM
Green
D K
DK
Allshire
R C
RC
D000236:Adenoma / Q000235:genetics; D000375:Aging / Q000235:genetics*; D001345:Autoradiography; D002277:Carcinoma / Q000235:genetics; D002455:Cell Division; D002875:Chromosomes / Q000648:ultrastructure*; D015179:Colorectal Neoplasms / Q000235:genetics*; D004247:DNA / Q000097:blood / Q000235:genetics / Q000378:metabolism; D004253:DNA Nucleotidylexotransferase / Q000378:metabolism; D015252:Deoxyribonucleases, Type II Site-Specific; D006801:Humans; D007413:Intestinal Mucosa / Q000032:analysis; D009693:Nucleic Acid Hybridization; D015345:Oligonucleotide Probes; D012091:Repetitive Sequences, Nucleic Acid
D015345:Oligonucleotide Probes; D004247:DNA; D004253:DNA Nucleotidylexotransferase; C024669:endodeoxyribonuclease AluI; D015252:Deoxyribonucleases, Type II Site-Specific; C032229:GANTC-specific type II deoxyribonucleases