Document Detail

Human somatic cell mutagenesis creates genetically tractable sarcomas.
MedLine Citation:
PMID:  25129143     Owner:  NLM     Status:  Publisher    
Creating spontaneous yet genetically tractable human tumors from normal cells presents a fundamental challenge. Here we combined retroviral and transposon insertional mutagenesis to enable cancer gene discovery starting with human primary cells. We used lentiviruses to seed gain- and loss-of-function gene disruption elements, which were further deployed by Sleeping Beauty transposons throughout the genome of human bone explant mesenchymal cells. De novo tumors generated rapidly in this context were high-grade myxofibrosarcomas. Tumor insertion sites were enriched in recurrent somatic copy-number aberration regions from multiple cancer types and could be used to pinpoint new driver genes that sustain somatic alterations in patients. We identified HDLBP, which encodes the RNA-binding protein vigilin, as a candidate tumor suppressor deleted at 2q37.3 in greater than one out of ten tumors across multiple tissues of origin. Hybrid viral-transposon systems may accelerate the functional annotation of cancer genomes by enabling insertional mutagenesis screens in higher eukaryotes that are not amenable to germline transgenesis.
Sam D Molyneux; Paul D Waterhouse; Dawne Shelton; Yang W Shao; Christopher M Watling; Qing-Lian Tang; Isaac S Harris; Brendan C Dickson; Pirashaanthy Tharmapalan; Geir K Sandve; Xiaoyang Zhang; Swneke D Bailey; Hal Berman; Jay S Wunder; Zsuzsanna Iszvak; Mathieu Lupien; Tak W Mak; Rama Khokha
Related Documents :
6405583 - Effect of 3'-methyl-n,n-dimethyl-4-aminoazobenzene in the presence or absence of liver ...
2842523 - A case of hepatocellular carcinoma with tumor thrombi in the epiploic vein.
21720473 - Metastatic carcinoid tumor obstructing left ventricular outflow.
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2014-8-17
Journal Detail:
Title:  Nature genetics     Volume:  -     ISSN:  1546-1718     ISO Abbreviation:  Nat. Genet.     Publication Date:  2014 Aug 
Date Detail:
Created Date:  2014-8-17     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9216904     Medline TA:  Nat Genet     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

Previous Document:  Predictors of 30-day acute kidney injury following radical and partial nephrectomy for renal cell ca...
Next Document:  JAGN1 deficiency causes aberrant myeloid cell homeostasis and congenital neutropenia.