Unknown,Transcriptomics,Genomics,Proteomics

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High-resolution genetic analysis of cancer cell lines with near normal karyotypes


ABSTRACT: Cancer development is associated with multiple genetic alterations and genomic instability either at the chromosomal or base pair level is generally thought to underlie these changes. However, it is still unknown whether genetic instability is absolutely required for tumorigenesis. Here we investigated the genomic instability status of four cytogenetically stable diploid cell lines CAL51, SK-UT-1B, A204 and CH1. We applied high resolution 500K single nucleotide polymorphism (SNP) array analysis and found that all the four cell lines have some sub-microscopic genomic copy number changes. Interestingly, there were many more sub-microscopic chromosome alterations in A204 and CH1 than in CAL51 and SK-UT-1B. Twenty-four-color fluorescence in situ hybridization (FISH) was used to analyse a large number of metaphases from CAL51, SK-UT-1B and CH1 cells. The rate of de novo chromosome rearrangements was significantly higher in CH1 than CAL51 and SK-UT-1B. Although this increased rate did not lead to many clonal cytogenetically apparent chromosome alterations in CH1 cells, it is consistent with a first step towards chromosomal instability. It is more striking that both cell lines CAL51 and SK-UT-1B which have a similar de novo chromosomal change rate to that of normal lymphocytes were microsatellite instability positive by BAT-26 microsatellite analysis. This study further strengths the current concept that genomic instability is associated with tumor development. Keywords: DNA copy number changes DNA from A204, CH1, CAL51 and SK-UT-1B were analyzed by Affymetrix Genechip Mapping 500K Set array. Data were compared with normal samples from HAPMAP database.

ORGANISM(S): Homo sapiens

SUBMITTER: Xueying Mao 

PROVIDER: E-GEOD-8649 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Subtle genomic alterations and genomic instability revealed in diploid cancer cell lines.

Mao Xueying X   Young Bryan D BD   Chaplin Tracy T   Shipley Janet J   Lu Yong-Jie YJ  

Cancer letters 20080414 1


To investigate if genomic instability exists in tumors with cytogenetically normal karyotypes, we analyzed four diploid cancer cell lines A204, CAL51, CH1 and SK-UT-1B. We detected subtle genomic changes in all four cell lines. More of these alterations were found in A204 and CH1 than in the microsatellite unstable lines CAL51 and SK-UT-1B. The number of de novo, non-clonal chromosome rearrangements was also significantly higher in CH1 than CAL51 and SK-UT-1B (p=0.001). This study reveals multip  ...[more]

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