PMID- 15677628
OWN - NLM
STAT- MEDLINE
DCOM- 20050608
LR  - 20091119
IS  - 0143-3334 (Print)
IS  - 0143-3334 (Linking)
VI  - 26
IP  - 5
DP  - 2005 May
TI  - Evidence that both genetic instability and selection contribute to the 
      accumulation of chromosome alterations in cancer.
PG  - 923-30
AB  - Cancer cells contain many genetic alterations, and genetic instability may be 
      important in tumourigenesis. We evaluated 58 breast and ovarian cancer cell lines 
      for microsatellite instability (MSI) and chromosomal instability (CIN). MSI was 
      identified in 3/33 breast and 5/25 ovarian cell lines, and 7/8 MSI lines showed 
      an inactivation of mismatch repair. Average ploidy by centromeric fluorescence in 
      situ hybridization (FISH) of MSI (n = 8, average ploidy = 2.65) and 
      microsatellite stable (MSS; n = 7, average ploidy = 3.01) cell lines was not 
      different, due to the presence of three aneuploid MSI lines, and two near-diploid 
      MSS lines. However, the variability of the centromeric FISH data was different 
      between MSI and MSS (P = 0.049). The complexity of structural chromosomal 
      rearrangements was not different between MSI and MSS. Thus, MSI and numerical CIN 
      are not mutually exclusive, and structural CIN occurs independently of MSI or 
      numerical CIN. Dynamic genetic instability was evaluated in three cell lines-MSI 
      diploid (MT-3), MSS diploid (SUM159) and MSS aneuploid (MT-1). Ten clones of each 
      of these cell lines were analysed by centromeric FISH and six-colour chromosome 
      painting. The variation in chromosome number was different among all three cell 
      lines (P < 0.001). MT-3 appeared numerically constant (94% of centromeric FISH 
      signals matched the mode). SUM159 was 88% constant; however, 7% of cells had 
      duplicated chromosomes. MT-1 was 82% constant; most changes were chromosomal 
      losses. The six-colour FISH data showed that SUM159 had more stable structural 
      chromosomal alterations (e.g. chromosomal translocations) compared with MT-3 and 
      MT-1, but had no increase in unstable changes (e.g. chromatid breaks) when 
      compared with MT-3. MT-1 had fewer unstable changes than both MT-3 and SUM159. 
      These data suggest that numerical CIN may contribute to aneuploidy, but that 
      selection plays an important role, particularly for the accumulation of 
      structural chromosomal changes.
FAU - Gorringe, Kylie L
AU  - Gorringe KL
AD  - Cancer Genomics Program, Department of Oncology, Hutchison/MRC Research Centre, 
      University of Cambridge, Cambridge CB2 2XZ, UK. kylie.gorringe@jcu.edu.au
FAU - Chin, Suet-Feung
AU  - Chin SF
FAU - Pharoah, Paul
AU  - Pharoah P
FAU - Staines, Joanne M
AU  - Staines JM
FAU - Oliveira, Carla
AU  - Oliveira C
FAU - Edwards, Paul A W
AU  - Edwards PA
FAU - Caldas, Carlos
AU  - Caldas C
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20050127
PL  - England
TA  - Carcinogenesis
JT  - Carcinogenesis
JID - 8008055
SB  - IM
MH  - Breast Neoplasms/genetics
MH  - *Chromosomal Instability
MH  - Chromosome Painting
MH  - DNA Mutational Analysis
MH  - DNA Repair/genetics
MH  - Female
MH  - Humans
MH  - Microsatellite Repeats/*genetics
MH  - Neoplasms/*genetics
MH  - Ovarian Neoplasms/genetics
MH  - *Selection, Genetic
EDAT- 2005/01/29 09:00
MHDA- 2005/06/09 09:00
CRDT- 2005/01/29 09:00
PHST- 2005/01/29 09:00 [pubmed]
PHST- 2005/06/09 09:00 [medline]
PHST- 2005/01/29 09:00 [entrez]
AID - bgi032 [pii]
AID - 10.1093/carcin/bgi032 [doi]
PST - ppublish
SO  - Carcinogenesis. 2005 May;26(5):923-30. doi: 10.1093/carcin/bgi032. Epub 2005 Jan 
      27.