PMID- 27520584
OWN - NLM
STAT- MEDLINE
DCOM- 20170126
LR  - 20171008
IS  - 1879-0038 (Electronic)
IS  - 0378-1119 (Linking)
VI  - 593
IP  - 1
DP  - 2016 Nov 15
TI  - Aneuploidy and asynchronous replication in non-alcholic fatty liver disease and 
      cryptogenic cirrhosis.
PG  - 162-166
LID - S0378-1119(16)30645-X [pii]
LID - 10.1016/j.gene.2016.08.017 [doi]
AB  - BACKGROUND/AIMS: 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. METHODOLOGY: 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.
CI  - Copyright (c) 2016 Elsevier B.V. All rights reserved.
FAU - Laish, Ido
AU  - Laish I
AD  - 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.
FAU - Mannasse-Green, Batya
AU  - Mannasse-Green B
AD  - Genetic Institute, Meir Medical Center, Kfar Saba, Israel.
FAU - Hadary, Ruth
AU  - Hadary R
AD  - Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel; Liver Unit, 
      Meir Medical Center, Kfar Saba, Israel.
FAU - Konikoff, Fred M
AU  - Konikoff FM
AD  - Gastroenterology and Hepatology Institute, Meir Medical Center, Kfar Saba, 
      Israel; Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel.
FAU - Amiel, Aliza
AU  - Amiel A
AD  - Genetic Institute, Meir Medical Center, Kfar Saba, Israel; Faculty of Life 
      Sciences, Bar Ilan University, Ramat Gan, Israel.
FAU - Kitay-Cohen, Yona
AU  - Kitay-Cohen Y
AD  - Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel; Liver Unit, 
      Meir Medical Center, Kfar Saba, Israel.
LA  - eng
PT  - Journal Article
DEP - 20160809
PL  - Netherlands
TA  - Gene
JT  - Gene
JID - 7706761
SB  - IM
MH  - Aged
MH  - *Alleles
MH  - *Aneuploidy
MH  - Cell Cycle/*genetics
MH  - *DNA Replication
MH  - Female
MH  - Humans
MH  - *Liver Cirrhosis/genetics/metabolism/pathology
MH  - Lymphocytes/metabolism/pathology
MH  - Male
MH  - Middle Aged
MH  - *Non-alcoholic Fatty Liver Disease/genetics/metabolism/pathology
MH  - *Telomere/genetics/metabolism
MH  - *Telomere Homeostasis
OTO - NOTNLM
OT  - Cryptogenic cirrhosis
OT  - FISH
OT  - Fatty liver
OT  - Telomeres
EDAT- 2016/08/16 06:00
MHDA- 2017/01/27 06:00
CRDT- 2016/08/14 06:00
PHST- 2016/02/21 00:00 [received]
PHST- 2016/07/24 00:00 [revised]
PHST- 2016/08/08 00:00 [accepted]
PHST- 2016/08/14 06:00 [entrez]
PHST- 2016/08/16 06:00 [pubmed]
PHST- 2017/01/27 06:00 [medline]
AID - S0378-1119(16)30645-X [pii]
AID - 10.1016/j.gene.2016.08.017 [doi]
PST - ppublish
SO  - Gene. 2016 Nov 15;593(1):162-166. doi: 10.1016/j.gene.2016.08.017. Epub 2016 Aug 
      9.