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Genetic signature of histiocytic sarcoma revealed by a sleeping beauty transposon genetic screen in mice.

PloS one | 2014

Histiocytic sarcoma is a rare, aggressive neoplasm that responds poorly to therapy. Histiocytic sarcoma is thought to arise from macrophage precursor cells via genetic changes that are largely undefined. To improve our understanding of the etiology of histiocytic sarcoma we conducted a forward genetic screen in mice using the Sleeping Beauty transposon as a mutagen to identify genetic drivers of histiocytic sarcoma. Sleeping Beauty mutagenesis was targeted to myeloid lineage cells using the Lysozyme2 promoter. Mice with activated Sleeping Beauty mutagenesis had significantly shortened lifespan and the majority of these mice developed tumors resembling human histiocytic sarcoma. Analysis of transposon insertions identified 27 common insertion sites containing 28 candidate cancer genes. Several of these genes are known drivers of hematological neoplasms, like Raf1, Fli1, and Mitf, while others are well-known cancer genes, including Nf1, Myc, Jak2, and Pten. Importantly, several new potential drivers of histiocytic sarcoma were identified and could serve as targets for therapy for histiocytic sarcoma patients.

Pubmed ID: 24827933 RIS Download

Associated grants

  • Agency: NCI NIH HHS, United States
    Id: 4R00CA151672-02
  • Agency: NCI NIH HHS, United States
    Id: R00 CA151672
  • Agency: NIBIB NIH HHS, United States
    Id: T32 EB008389
  • Agency: NCI NIH HHS, United States
    Id: P30 CA077598
  • Agency: NIBIB NIH HHS, United States
    Id: T32EB008389
  • Agency: NCI NIH HHS, United States
    Id: R01 CA113636

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Primer3 (tool)

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RRID:SCR_008117

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RRID:SCR_011784

Non profit research organization for genome sequences to advance understanding of biology of humans and pathogens in order to improve human health globally. Provides data which can be translated for diagnostics, treatments or therapies including over 100 finished genomes, which can be downloaded. Data are publicly available on limited basis, and provided more extensively upon request.

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RRID:SCR_002260

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Some key features of COSMIC are:
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RRID:IMSR_JAX:004781

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