Gene fusions by chromothripsis of chromosome 5q in the VCaP prostate cancer cell line

The VCaP cell line is widely used in prostate cancer research as it is a unique model to study castrate resistant disease expressing high levels of the wild type androgen receptor and the TMPRSS2 - ERG fusion transcript. Using next generation sequencing, we assembled the structural variations in VCa...

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Bibliographic Details
Published in:Human genetics 2013-06, Vol.132 (6), p.709-713
Main Authors: Teles Alves, Inês, Hiltemann, Saskia, Hartjes, Thomas, van der Spek, Peter, Stubbs, Andrew, Trapman, Jan, Jenster, Guido
Format: Article
Language:English
Subjects:
Androgens
Biomedical and Life Sciences
Biomedicine
Cancer
Cell Line, Tumor
Chromosomes
Chromosomes, Human, Pair 5 - genetics
DNA
Gene Dosage
Gene Function
Gene Fusion
Gene Rearrangement
Genes
Genetic aspects
Genetic research
Genomes
Heterozygote
Human Genetics
Humans
Male
Medical research
Metabolic Diseases
Molecular Medicine
Prostate cancer
Prostatic Neoplasms - genetics
RNA
Short Report
Toy industry
Translocation, Genetic
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Summary:The VCaP cell line is widely used in prostate cancer research as it is a unique model to study castrate resistant disease expressing high levels of the wild type androgen receptor and the TMPRSS2 - ERG fusion transcript. Using next generation sequencing, we assembled the structural variations in VCaP genomic DNA and observed a massive number of genomic rearrangements along the q arm of chromosome 5, characteristic of chromothripsis. Chromothripsis is a recently recognized phenomenon characterized by extensive chromosomal shattering in a single catastrophic event, mainly detected in cancer cells. Various structural events identified on chromosome 5q of VCaP resulted in gene fusions. Out of the 18 gene fusion candidates tested, 15 were confirmed on genomic level. In our set of gene fusions, only rarely we observe microhomology flanking the breakpoints. On RNA level, only five transcripts were detected and NDUFAF2 - MAST4 was the only resulting in an in-frame fusion transcript. Our data indicate that although a marker of genomic instability, chromothripsis might lead to only a limited number of functionally relevant fusion genes.
ISSN:0340-6717
1432-1203
DOI:10.1007/s00439-013-1308-1