title: Aneuploidy and asynchronous replication in non-alcholic fatty liver disease and cryptogenic cirrhosis.
abstract: OBJECTIVE
  Non-alcoholic fatty liver disease (NAFLD) and cryptogenic cirrhosis (CC), which is largely a late sequela of NAFLD, are considered pre-neoplastic conditions that might progress to hepatocellular carcinoma. Aneuploidy, telomere aggregates and synchronization of replication were evaluated as markers of genetic instability in these patients.
  
  
  METHODS
  Peripheral blood lymphocytes from 22 patients with NAFLD, 20 patients with CC and 20 age-matched healthy controls were analyzed. To determine random aneuploidy, we used the fluorescence in situ hybridization (FISH) with probes for chromosomes 9 and 18. The rate of aneuploidy was inferred from the fraction of cells revealing one, three or more hybridization signals per cell. Aggregate size was divided into three fusion groups of 2-5, 6-10 and 11-15 telomeres, relative to the size of a single telomere. The replication pattern was determined by FISH in two pairs of alleles, 15qter and 13qter. Asynchrony was determined by the presence of one single and one set of double dots in the same cell.
  
  
  RESULTS
  Significantly higher random aneuploidy rate was found in the CC patients than in the control group, and to a lesser degree in NAFLD patients. Telomere aggregates were insignificantly higher in both groups. Only patients with CC showed significantly higher rate of asynchronous replication with proportionately more cells with two single dots among the normal cells (p<0.001).
  
  
  CONCLUSIONS
  These results likely reflect changes in gene replication and cell cycle progression in these conditions, possibly correlating with their malignant potential.
authors: Gastroenterology and Hepatology Institute, Meir Medical Center, Kfar Saba, Israel; Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel. Electronic address: ido.laish@gmail.com.
authors: Ido
authors: I
authors: Laish
authors: Genetic Institute, Meir Medical Center, Kfar Saba, Israel.
authors: Batya
authors: B
authors: Mannasse-Green
authors: Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel; Liver Unit, Meir Medical Center, Kfar Saba, Israel.
authors: Ruth
authors: R
authors: Hadary
authors: Gastroenterology and Hepatology Institute, Meir Medical Center, Kfar Saba, Israel; Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel.
authors: Fred M
authors: FM
authors: Konikoff
authors: Genetic Institute, Meir Medical Center, Kfar Saba, Israel; Faculty of Life Sciences, Bar Ilan University, Ramat Gan, Israel.
authors: Aliza
authors: A
authors: Amiel
authors: Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel; Liver Unit, Meir Medical Center, Kfar Saba, Israel.
authors: Yona
authors: Y
authors: Kitay-Cohen
mesh_terms: D000368:Aged; D000483:Alleles; D000782:Aneuploidy; D002453:Cell Cycle / Q000235:genetics*; D004261:DNA Replication; D005260:Female; D006801:Humans; D008103:Liver Cirrhosis / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D008214:Lymphocytes / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D065626:Non-alcoholic Fatty Liver Disease / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D016615:Telomere / Q000235:genetics / Q000378:metabolism; D059505:Telomere Homeostasis
keywords: Cryptogenic cirrhosis; FISH; Fatty liver; Telomeres