Journal Article

Evidence that both genetic instability and selection contribute to the accumulation of chromosome alterations in cancer

Kylie L. Gorringe, Suet-Feung Chin, Paul Pharoah, Joanne M. Staines, Carla Oliveira, Paul A.W. Edwards and Carlos Caldas

in Carcinogenesis

Volume 26, issue 5, pages 923-930
Published in print May 2005 | ISSN: 0143-3334
Published online January 2005 | e-ISSN: 1460-2180 | DOI: http://dx.doi.org/10.1093/carcin/bgi032
Evidence that both genetic instability and selection contribute to the accumulation of chromosome alterations in cancer

More Like This

Show all results sharing this subject:

  • Clinical Cytogenetics and Molecular Genetics

GO

Show Summary Details

Preview

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.

Keywords: ATCC, American Type Culture Collection; CGH, comparative genomic hybridization; CIN, chromosome instability; FISH, fluorescence in situ hybridization; MMR, mismatch repair; MSI, microsatellite instability; MSS, microsatellite stability; PCR, polymerase chain reaction; SKY, spectral karyotyping

Journal Article.  6400 words.  Illustrated.

Subjects: Clinical Cytogenetics and Molecular Genetics

Full text: subscription required

How to subscribe Recommend to my Librarian

Users without a subscription are not able to see the full content. Please, subscribe or login to access all content.