PMID- 14745031
OWN - NLM
STAT- MEDLINE
DCOM- 20040309
LR  - 20231105
IS  - 0027-8424 (Print)
IS  - 1091-6490 (Electronic)
IS  - 0027-8424 (Linking)
VI  - 101
IP  - 5
DP  - 2004 Feb 3
TI  - Induction of aneuploidy by increasing chromosomal instability during 
      dedifferentiation of hepatocellular carcinoma.
PG  - 1309-14
AB  - To gain more insight into the role of chromosomal instability (CIN), the 
      cytogenetic hallmark of most solid tumors, we performed fluorescence in situ 
      hybridization (FISH) on interphase nuclei of cytological specimens enabling the 
      correct detection of chromosome copies in intact tumor cells of 18 well (G1), 
      moderately (G2), or poorly (G3) differentiated hepatocellular carcinomas (HCCs). 
      A close correlation between the morphological dedifferentiation and increasing 
      copy numbers and variation of FISH signals was seen for chromosomes 1 and 8, 
      respectively (P < or = 0.0002). Four HCC G1 had constant chromosome patterns for 
      chromosomes 1 and/or 8 with a mean of signals per nucleus < or =5.08 and < or =3 
      different signal combinations, indicating a low level of CIN, as confirmed by 
      FISH using probes for centromeres of chromosomes 3, 7, and 17. In contrast to 
      this, five HCC G2-3 revealed > or =8.46 signals per nucleus and 23-41 different 
      signal combinations, indicating high levels of CIN. In the remaining cases, 
      signal counts from 5.96-8.46 and 7-15 combinations were seen. Here, nuclei with 
      constant aberration patterns and low copy numbers occurred alongside nuclei with 
      inconstant patterns and high copy numbers. It is evident that in these cases a 
      transition from well to moderately differentiated HCC developed in parallel to an 
      increase in CIN, possibly induced by a major dysregulation of mitotic control 
      mechanisms. In conclusion, CIN may induce a stepwise increase of aneuploidy in 
      HCC that is mirrored by the morphological dedifferentiation of tumor cells.
FAU - Wilkens, Ludwig
AU  - Wilkens L
AD  - Institutes of Cell and Molecular Pathology and Pathology, Hannover Medical 
      School, Carl-Neuberg-Strasse 1, 30625 Hannover, Germany. 
      wilkens.ludwig@mh-hannover.de
FAU - Flemming, Peer
AU  - Flemming P
FAU - Gebel, Michael
AU  - Gebel M
FAU - Bleck, Joerg
AU  - Bleck J
FAU - Terkamp, Christof
AU  - Terkamp C
FAU - Wingen, Luzie
AU  - Wingen L
FAU - Kreipe, Hans
AU  - Kreipe H
FAU - Schlegelberger, Brigitte
AU  - Schlegelberger B
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20040126
PL  - United States
TA  - Proc Natl Acad Sci U S A
JT  - Proceedings of the National Academy of Sciences of the United States of America
JID - 7505876
SB  - IM
MH  - Aged
MH  - *Aneuploidy
MH  - Carcinoma, Hepatocellular/*genetics/pathology
MH  - Cell Differentiation
MH  - *Chromosomal Instability
MH  - Female
MH  - Humans
MH  - In Situ Hybridization, Fluorescence
MH  - Liver Neoplasms/*genetics/pathology
MH  - Male
MH  - Middle Aged
PMC - PMC337049
EDAT- 2004/01/28 05:00
MHDA- 2004/03/10 05:00
PMCR- 2004/08/03
CRDT- 2004/01/28 05:00
PHST- 2004/01/28 05:00 [pubmed]
PHST- 2004/03/10 05:00 [medline]
PHST- 2004/01/28 05:00 [entrez]
PHST- 2004/08/03 00:00 [pmc-release]
AID - 0305817101 [pii]
AID - 1011309 [pii]
AID - 10.1073/pnas.0305817101 [doi]
PST - ppublish
SO  - Proc Natl Acad Sci U S A. 2004 Feb 3;101(5):1309-14. doi: 
      10.1073/pnas.0305817101. Epub 2004 Jan 26.