| First Author | Bender AM | Year | 2010 |
| Journal | Cancer Res | Volume | 70 |
| Issue | 9 | Pages | 3557-65 |
| PubMed ID | 20388773 | Mgi Jnum | J:159371 |
| Mgi Id | MGI:4442518 | Doi | 10.1158/0008-5472.CAN-09-4674 |
| Citation | Bender AM, et al. (2010) Sleeping beauty-mediated somatic mutagenesis implicates CSF1 in the formation of high-grade astrocytomas. Cancer Res 70(9):3557-65 |
| abstractText | 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. |
