Relationship between telomere shortening, genetic instability, and site of tumour origin in colorectal cancers.
BACKGROUND
Telomeres, located at chromosome ends, are progressively shortened during each cell cycle by replication-dependent loss of DNA termini. Although maintenance of telomere length is critical for cell-replicative potential and tumourigenesis, the erosion of telomeres can lead to genetic instability, a pivotal mechanism in the neoplastic process.


METHODS
A total of 118 colorectal cancer (CRC) samples (53 right-colon, 30 left-colon, and 35 rectal tumours) and corresponding adjacent non-cancerous tissues were evaluated for telomere length, p53 mutation, and microsatellite instability (MSI). Telomere length was estimated by real-time PCR.


RESULTS
Telomeres were significantly shorter in CRCs than in adjacent tissues, regardless of tumour stage and grade, site, or genetic alterations (P<0.0001). Moreover, in normal tissues, but not in tumours, telomere length inversely correlated with age (r=-0.24, P=0.017). Telomere length in CRCs did not differ with tumour progression or p53 status; however, in CRCs carrying the wild-type p53, telomeres were significantly shorter in tumours with MSI than in those with stable microsatellites (P=0.027). Furthermore, telomere length differed according to tumour location, being longer in rectal cancers (P=0.03).


CONCLUSIONS
These findings suggest that telomere shortening is a key initial event in colorectal carcinogenesis. The extent of telomere erosion is related to tumour origin site and may be influenced by the mismatch repair pathway.
Rampazzo
E
E
Department of Oncology and Surgical Sciences, University of Padova, Italy.
Bertorelle
R
R
Serra
L
L
Terrin
L
L
Candiotto
C
C
Pucciarelli
S
S
Del Bianco
P
P
Nitti
D
D
De Rossi
A
A
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000473:pathology*; D005260:Female; D042822:Genomic Instability; D006801:Humans; D007413:Intestinal Mucosa / Q000648:ultrastructure; D008297:Male; D008875:Middle Aged; D019098:Telomerase / Q000037:antagonists & inhibitors / Q000378:metabolism; D016615:Telomere / Q000473:pathology*
C509186:TERT protein, human; D019098:Telomerase
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