Document Detail


Gene fusions by chromothripsis of chromosome 5q in the VCaP prostate cancer cell line.
MedLine Citation:
PMID:  23615946     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
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.
Authors:
Inês Teles Alves; Saskia Hiltemann; Thomas Hartjes; Peter van der Spek; Andrew Stubbs; Jan Trapman; Guido Jenster
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2013-4-25
Journal Detail:
Title:  Human genetics     Volume:  -     ISSN:  1432-1203     ISO Abbreviation:  Hum. Genet.     Publication Date:  2013 Apr 
Date Detail:
Created Date:  2013-4-25     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  7613873     Medline TA:  Hum Genet     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
Department of Urology, Josephine Nefkens Institute, Erasmus University Medical Center, Be 362a, P.O. Box 2040, 3000 CA, Rotterdam, The Netherlands, i.telesalves@erasmusmc.nl.
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