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Sleeping Beauty-Mediated Somatic Mutagenesis Implicates CSF1 in the Formation of High-Grade Astrocytomas

  1. Author:
    Bender, A. M.
    Collier, L. S.
    Rodriguez, F. J.
    Tieu, C.
    Larson, J. D.
    Halder, C.
    Mahlum, E.
    Kollmeyer, T. M.
    Akagi, K.
    Sarkar, G.
    Largaespada, D. A.
    Jenkins, R. B.

  2. Author Address

    [Bender, Aaron M.; Rodriguez, Fausto J.; Tieu, Christina; Halder, Chandralekha; Mahlum, Eric; Kollmeyer, Thomas M.; Sarkar, Gobinda; Jenkins, Robert B.] Mayo Clin, Dept Lab Med & Pathol, Rochester, MN 55905 USA. [Collier, Lara S.] Univ Wisconsin, Sch Pharm, Div Pharmaceut Sci, Madison, WI 53706 USA. [Larson, Jon D.; Largaespada, David A.] Univ Minnesota, Arnold & Mabel Beckman Ctr Genome Engn, Minneapolis, MN USA. [Larson, Jon D.; Largaespada, David A.] Univ Minnesota, Mason Canc Ctr, Minneapolis, MN USA. [Akagi, Keiko] NCI, Mouse Canc Genet Program, Frederick, MD 21701 USA. [Akagi, Keiko] Ohio State Univ, Ctr Comprehens Canc, Columbus, OH 43210 USA.;Jenkins, RB, Mayo Clin, Dept Lab Med & Pathol, Hilton 9-71,150 3rd St SW, Rochester, MN 55905 USA.;rjenkins@mayo.edu
    1. Year: 2010
    2. Date: May
  2. Journal: Cancer Research
    1. 70
    2. 9
    3. Pages: 3557-3565
  4. Type of Article: Article
  5. ISSN: 0008-5472
  1. Abstract:

    The Sleeping Beauty (SB) transposon system has been used as an insertional mutagenesis tool to identify novel cancer genes. To identify glioma-associated genes, we evaluated tumor formation in the brain tissue from 117 transgenic mice that had undergone constitutive SB-mediated transposition. Upon analysis, 21 samples (18%) contained neoplastic tissue with features of high-grade astrocytomas. These tumors expressed glial markers and were histologically similar to human glioma. Genomic DNA from SB-induced astrocytoma tissue was extracted and transposon insertion sites were identified. Insertions in the growth factor gene Csf1 were found in 13 of the 21 tumors (62%), clustered in introns 5 and 8. Using reverse transcription-PCR, we documented increased Csf1 RNAs in tumor versus adjacent normal tissue, with the identification of transposon-terminated Csf1 mRNAs in astrocytomas with SB insertions in intron 8. Analysis of human glioblastomas revealed increased levels of Csf1 RNA and protein. Together, these results indicate that SB-insertional mutagenesis can identify high-grade astrocytoma-associated genes and they imply an important role for CSF1 in the development of these tumors. Cancer Res; 70(9); 3557-65. (C) 2010 AACR.

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External Sources

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  2. DOI: 10.1158/0008-5472.can-09-4674
  3. View record in Web of Science®
  4. WOS: 000278486200015

Library Notes

  1. Fiscal Year: FY2009-2010
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