The structural nature of chromosomal instability in colon cancer cells

Biological and genetic cell heterogeneity is a landmark of most colorectal cancers and provides a frame for tumor progression as an evolutional process. Classical models have hypothesized that increased genetic instability may contribute to modulating and shaping malignant transformation. This is tr...

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Bibliographic Details
Published in:The FASEB journal 2003-02, Vol.17 (2), p.289-291
Main Authors: Ribas, Maria, Masramon, Laia, Aiza, Gemma, Capellà, Gabriel, Miró, Rosa, Peinado, Miguel A.
Format: Article
Language:English
Subjects:
chromosomal rearrangements
Chromosome Aberrations
Colonic Neoplasms - genetics
Colonic Neoplasms - pathology
colorectal cancer
Cytogenetic Analysis - methods
genomic damage
genomic instability
Humans
Tumor Cells, Cultured
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Summary:Biological and genetic cell heterogeneity is a landmark of most colorectal cancers and provides a frame for tumor progression as an evolutional process. Classical models have hypothesized that increased genetic instability may contribute to modulating and shaping malignant transformation. This is true for the small subset of colorectal cancers displaying microsatellite instability. For the rest of colorectal tumors, numerical and/or structural chromosomal alterations are the most prominent outcome of genetic disruption. These observations have prompted some investigators to hypothesize about the presence of chromosomal instability in these cells. To characterize chromosomal instability in cancer cells, we have analyzed genetic clonal divergence in three colorectal cancer cell lines considered to be archetypes in cancer research (HCT116, LoVo, and SW480). A dynamic setting was designed to allow the calculation of mutation rates. Comprehensive analyses at the chromosomal level revealed distinctive patterns of genetic divergence. Aneuploid SW480 cells displayed high rates of structural alterations (>100‐fold) as compared with near diploid LoVo cells. Numerical alterations also occurred more frequently in SW480 cells but at low rates as compared with rearrangements in the chromosomically unstable SW480 cells. These results strengthen the role of structural instability in the generation of genetic heterogeneity in colorectal cancer.
ISSN:0892-6638
1530-6860
DOI:10.1096/fj.02-0425fje