TITLE

Chromosomal instability in ulcerative colitis is related to telomere shortening

AUTHOR(S)
O'Sullivan, Jacintha N.; Bronner, Mary P.; Brentnall, Teresa A.; Finley, Jennifer C.; Shen, Wen-Tang; Emerson, Scott; Emond, Mary J.; Gollahon, Katherine A.; Moskovitz, Alexander H.; Crispin, David A.; Potter, John D.; Rabinovitch, Peter S.
PUB. DATE
October 2002
SOURCE
Nature Genetics;Oct2002, Vol. 32 Issue 2, p280
SOURCE TYPE
Academic Journal
DOC. TYPE
Article
ABSTRACT
Ulcerative colitis, a chronic inflammatory disease of the colon, is associated with a high risk of colorectal carcinoma that is thought to develop through genomic instability. We considered that the rapid cell turnover and oxidative injury observed in ulcerative colitis might accelerate telomere shortening, thereby increasing the potential of chromosomal ends to fuse, resulting in cycles of chromatin bridge breakage and fusion and chromosomal instability associated with tumor cell progression. Here we have used quantitative fluorescence in situ hybridization to compare chromosomal aberrations and telomere shortening in non-dysplastic mucosa taken from individuals affected by ulcerative colitis, either with (UC progressors) or without (UC non-progressors) dysplasia or cancer. Losses, but not gains, of chromosomal arms and centromeres are highly correlated with telomere shortening. Chromosomal losses are greater and telomeres are shorter in biopsy samples from UC progressors than in those from UC non-progressors or control individuals without ulcerative colitis. A mechanistic link between telomere shortening and chromosomal instability is supported by a higher frequency of anaphase bridges—an intermediate in the breakage and fusion of chromatin bridges—in UC progressors than in UC non-progressors or control individuals. Our study shows that telomere length is correlated with chromosomal instability in a precursor of human cancer.
ACCESSION #
7503247

 

Related Articles

  • Telomere shortening correlates to dysplasia but not to DNA aneuploidy in longstanding ulcerative colitis. Friis-Ottessen, Mariann; Bendix, Laila; Kølvraa, Steen; Norheim-Andersen, Solveig; De Angelis, Paula M.; Clausen, Ole Petter F. // BMC Gastroenterology;2014, Vol. 14 Issue 1, p1 

    Background Ulcerative colitis (UC) is a chronic, inflammatory bowel disease which may lead to dysplasia and adenocarcinoma in patients when long-lasting. Short telomeres have been reported in mucosal cells of UC patients. Telomeres are repetitive base sequences capping the ends of linear...

  • Telomere shortening in the colonic mucosa of patients with ulcerative colitis. Kinouchi, Yoshitaka; Hiwatashi, Nobuo; Chida, Masaki; Nagashima, Fumio; Takagi, Sho; Maekawa, Hiroki; Toyota, Takayoshi; Kinouchi, Y; Hiwatashi, N; Chida, M; Nagashima, F; Takagi, S; Maekawa, H; Toyota, T // Journal of Gastroenterology;1998, Vol. 33 Issue 3, p343 

    Telomere length in human somatic cells gradually decreases with the number of cell divisions and is regarded as a marker of somatic cell turnover. Mucosal cells of the affected colon show rapid turnover in individuals with active ulcerative colitis (UC). Telomere length was determined by...

  • Genome-wide association study for ulcerative colitis identifies risk loci at 7q22 and 22q13 (IL17REL). Franke, Andre; Balschun, Tobias; Sina, Christian; Ellinghaus, David; Häsler, Robert; Mayr, Gabriele; Albrecht, Mario; Wittig, Michael; Buchert, Eva; Nikolaus, Susanna; Gieger, Christian; Wichmann, H. Erich; Sventoraityte, Jurgita; Kupcinskas, Limas; Onnie, Clive M.; Gazouli, Maria; Anagnou, Nicholas P.; Strachan, David; McArdle, Wendy L.; Mathew, Christopher G. // Nature Genetics;Apr2010, Vol. 42 Issue 4, p292 

    We performed a genome-wide association analysis of 1,897,764 SNPs in 1,043 German ulcerative colitis (UC) cases and 1,703 controls. We discovered new associations at chromosome 7q22 (rs7809799) and at chromosome 22q13 in IL17REL (rs5771069) and confirmed these associations in six replication...

  • Linkage of ulcerative colitis to the pericentromeric region of chromosome 16 in Italian inflammatory bowel disease families is independent of the presence of common CARD14 mutations. Annese, V.; Latiano, A.; Palmieri, O.; Li, H.-H.; Forabosco, P.; Ferraris, A.; Andriulli, A.; Vecchi, M.; Ardizzone, S.; Cottone, M.; Dallapiccola, B.; Rappaport, E.; Fortina, P.; Devoto, M. // Journal of Medical Genetics;Nov2003, Vol. 40 Issue 11, p837 

    Focuses on the linkage of ulcerative colitis to the pericentromeric region of chromosome 16 in Italian inflammatory bowel disease (IBD) families. Presence of common CARD14 mutations; Alleleic variants of single nucleotide polymorphisms; Risk of IBD.

  • Sequence variants in IL10, ARPC2 and multiple other loci contribute to ulcerative colitis susceptibility. Franke, Andre; Balschun, Tobias; Karlsen, Tom H; Sventoraityte, Jurgita; Nikolaus, Susanna; Mayr, Gabriele; Domingues, Francisco S; Albrecht, Mario; Nothnagel, Michael; Ellinghaus, David; Sina, Christian; Onnie, Clive M; Weersma, Rinse K; Stokkers, Pieter C F; Wijmenga, Cisca; Gazouli, Maria; Strachan, David; McArdle, Wendy L; Vermeire, Séverine; Rutgeerts, Paul // Nature Genetics;Nov2008, Vol. 40 Issue 11, p1319 

    Inflammatory bowel disease (IBD) typically manifests as either ulcerative colitis (UC) or Crohn's disease (CD). Systematic identification of susceptibility genes for IBD has thus far focused mainly on CD, and little is known about the genetic architecture of UC. Here we report a genome-wide...

  • Novel Genetic Risk Markers for Ulcerative Colitis in the IL2/IL21 Region Are in Epistasis With IL23R and Suggest a Common Genetic Background for Ulcerative Colitis and Celiac Disease. Glas, Jürgen; Stallhofer, Johannes; Ripke, Stephan; Wetzke, Martin; Pfennig, Simone; Klein, Wolfram; Epplen, Jörg T.; Griga, Thomas; Schiemann, Uwe; Lacher, Martin; Koletzko, Sibylle; Folwaczny, Matthias; Lohse, Peter; Göke, Burkhard; Ochsenkühn, Thomas; Müller-Myhsok, Bertram; Brand, Stephan // American Journal of Gastroenterology;Jul2009, Vol. 104 Issue 7, p1737 

    OBJECTIVES:Recently, a genome-wide association study showed that single-nucleotide polymorphisms (SNPs) in the chromosome 4q27 region containing IL2 and IL21 are associated with celiac disease. Given the increased prevalence of inflammatory bowel disease (IBD) among celiac disease patients, we...

  • Serendipitous Neologisms. Rosenbloom, Arlan L. // Clinical Pediatrics;Sep1972, Vol. 11 Issue 9, p496 

    Defines several medical terms and phrases. Ulcerative colitis; Ultimate short stature; Capillary fragility; Karyotype; Chromosomal deletion; Femoral vein Erythroblastosis fetalis.

  • Ménétrier's disease and severe gastric ulcers associated with cytomegalovirus infection in an immunocompetent child: a case report. Canan, Oğuz; Özçay, Figen; Bilezikçi, Banu // Turkish Journal of Pediatrics;2008, Vol. 50 Issue 3, p291 

    In pediatric patients, Ménétrier's disease is an uncommon clinical entity that has been rarely described only as sporadic cases, and the etiology is unclear. These patients usually have a self-limiting clinical course. Cytomegalovirus is an important pathogen in the immunocompromised host....

  • Genotype-phenotype analysis of the Crohn's disease susceptibility haplotype on chromosome 5q31. Armuzzi, A.; Ahmad, T.; Ling, K.-L.; de Silva, A.; Cullen, S.; van Heel, D.; Orchard, T.R.; Welsh, K.I.; Marshall, S.E.; Jewell, D.P. // Gut;Aug2003, Vol. 52 Issue 8, p1133 

    Background and aims: Recent molecular data suggest that genetic factors may underlie the disease heterogeneity observed in both ulcerative colitis (UC) and Crohn's disease (CD). A locus on chromosome 5q has been implicated in susceptibility to CD, and recently refined by linkage disequilibrium...

Share

Read the Article

Courtesy of THE LIBRARY OF VIRGINIA

Sorry, but this item is not currently available from your library.

Try another library?
Sign out of this library

Other Topics