Increased TERC gene copy number and cells in senescence in primary sclerosing cholangitis compared to colitis and control patients.
OBJECTIVE
Primary sclerosing cholangitis (PSC) is a chronic cholestatic disorder that involves inflammatory and fibrotic changes in the bile ducts. Up to 80% of patients have concomitant inflammatory bowel disease (IBD) with colitis. PSC patients are predisposed to develop hepatobiliary, colonic and other extrahepatic malignancies, probably related to inflammatory processes that might promote carcinogenesis. Telomerase is an enzyme complex that lengthens telomeres and has enhanced expression in numerous malignancies. In this study, we evaluated the TERC gene copy number, the proportion of cells in senescence and the amount of fragmentation in the senescent state.


METHODS
Fluorescence in situ hybridization (FISH) for the TERC gene was applied to lymphocytes retrieved from PSC (N=19), colitis (N=20) and healthy control patients (N=20) to determine the TERC copy number. On the same FISH slides, cells stained with DAPI were also analyzed for senescence-associated heterochromatin foci (SAHF) status, including the number of cells with fragments and the number of SAHF fragments in each cell.


RESULTS
A higher TERC gene copy number was observed in cells from PSC patients compared to colitis and control group patients. It was also higher in the colitis than in the control group. Significantly more cells in the senescent state and more fragmentation in each cell were observed in the PSC group compared to colitis and control groups.


CONCLUSIONS
The TERC gene copy number and the number of cells in the senescent state were increased in PSC patients compared to the colitis and control groups. These findings are probably related to the genetic instability parameters that reflect the higher tendency of this patient group to develop malignancies.
Gastroenterology and Hepatology Institute, Meir Medical Center, Kfar Saba, Israel.
Ido
I
Laish
Hila
H
Katz
Yael
Y
Sulayev
Meytal
M
Liberman
Timna
T
Naftali
Fabiana
F
Benjaminov
Assaf
A
Stein
Yona
Y
Kitay-Cohen
Tal
T
Biron-Shental
Fred
F
Konikoff
Aliza
A
Amiel
D016022:Case-Control Studies; D016922:Cellular Senescence; D015209:Cholangitis, Sclerosing / Q000235:genetics* / Q000473:pathology; D003093:Colitis, Ulcerative / Q000235:genetics* / Q000473:pathology; D005260:Female; D018628:Gene Dosage; D006801:Humans; D008297:Male; D008875:Middle Aged; D012313:RNA / Q000235:genetics*; D019098:Telomerase / Q000235:genetics*
C422952:telomerase RNA; D012313:RNA; D019098:Telomerase
4,6 diamidino-2phenylindole; C-reactive protein; CD; CRC; CRP; Crohn's disease; DAPI; DDR; DNA damage response; FISH; HBI; Harvey–Bradshaw index; IBD; PBS; PSC; Primary sclerosing cholangitis; RNA template; SAHF; Senescence; TERC; TERC gene, 3q26; Telomerase; UC; Ulcerative colitis; colorectal carcinoma; fluorescence in situ hybridization; hTERT; hTR; human telomerase reverse transcriptase; inflammatory bowel disease; phosphate buffered saline; primary sclerosing cholangitis; senescence-associated heterochromatin foci; ulcerative colitis