Telomere reduction in human colorectal carcinoma and with ageing

Abstract

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.

Telomere length variation in biliary tract metaplasia, dysplasia, and carcinoma

“…17,18,30 Shortened telomeres have been identified in a variety of invasive cancers and preinvasive lesions of the pancreas and prostate, and telomere shortening may be a critical early event in the development of epithelial neoplasms. 13,14,31,32 In addition to telomere shortening observed in dysplastic and carcinoma specimens, the majority of metaplastic lesions of the gallbladder in this study also demonstrated telomere shortening, supporting prior genetic evidence that metaplastic change in the gallbladder represents an early neoplastic alteration. 7 Specifically, in the study of Wistuba et al, 7 gallbladder metaplasias showed loss of heterozygosity in at least one cancer-associated locus in four of five cases.…”

Telomerase reverse transcriptase gene is a direct target of c-Myc but is not functionally equivalent in cellular transformation

“…Telomere attrition in the absence of telomerase has been shown to be an intrinsic timing mechanism that controls the number of somatic cell divisions prior to senescence (Harley et al, 1990;Hastie et al, 1990;Counter et al, 1992;Bodnar et al, 1998). The prominence of TERT in telomere homeostasis and the pro®le of TERT gene expression in normal and neoplastic settings prompted us to determine whether various cellular growth control and transcriptional factors regulate TERT gene expression and/or telomerase activity in primary human lung ®broblasts.…”

Telomerase activity and telomere length in pediatric patients with malignancies undergoing chemotherapy

“…[15][16][17][18][19][20][21][22][23][24][25][26][27][28][29][46][47][48][49] Previous studies in childhood and adult leukemia have suggested that telomerase activity and short tel-(one Ewing's sarcoma, one Wilms' tumor) revealed two peak TRF values at diagnosis (peak 1: 11.7 kbp, peak 2: 7.8 kbp)…”

“…From our (PD). 3,12,19,25,[56][57][58] In this study, we analyzed mean and peak values, since the acquisition of mean TRF values alone may results, one can hypothesize that telomere length shortening reflects a possible effect on all cells including somatic cells be inaccurate. In acute leukemia, most BM and PB specimens allowed the detection of two peaks: the longer corresponding which would then lead to premature aging, unless telomeres can recover, elongate and potentially gain their initial length to normal cells, correlating with telomeres of granulocyte controls, and the shorter peak corresponding to the leukemic after discontinuation of chemotherapy.…”