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Chromosome Preparation From Cultured Cells
Published on: January 28, 2014
Chromothripsis in Hodgkin lymphoma
Stefan Nagel1, Corinna Meyer, Hilmar Quentmeier
1Department of Human and Animal Cell Lines, Leibniz-Institute DSMZ--German Collection of Microorganisms and Cell Cultures, Braunschweig, Germany. sna@dsmz.de
Genes, Chromosomes & Cancer
|May 1, 2013
Summary
Chromosomal rearrangements called chromothripsis were found in Hodgkin lymphoma (HL) cell lines. These rearrangements caused ABL1 gene overexpression, leading to resistance against dasatinib treatment.
Area of Science:
- Oncology
- Genomics
- Cancer Biology
Background:
- Chromosomal rearrangements are hallmarks of cancer, often driving deregulated gene expression.
- Chromothripsis, a mechanism involving massive single-step genomic rearrangements, is an emerging oncogenic process.
Purpose of the Study:
- To document and characterize chromothripsis in Hodgkin lymphoma (HL) cell lines.
- To investigate the oncogenomic implications of chromothripsis in HL.
Main Methods:
- Genomic profiling of HL cell lines.
- Fluorescent in situ hybridization (FISH) analyses to identify chromosomal aberrations.
- Gene expression analysis and pharmacological sensitivity testing.
Main Results:
- Chromothripsis was identified in HL cell lines, characterized by alternating amplicons of specific chromosomal regions.
- In L-1236 cells, rearrangements involving chromosomes 3 and 9 led to ABL1 gene amplification and overexpression.
- Overexpression of ABL1 correlated with resistance to the kinase inhibitor dasatinib.
Conclusions:
- Chromothriptic rearrangements are present in Hodgkin lymphoma.
- These rearrangements can lead to oncogene overexpression and drug resistance, exemplified by ABL1 and dasatinib.
- HL cell lines with chromothripsis serve as valuable models for studying this oncogenomic mechanism.
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