Sleeping beauty-mediated somatic mutagenesis implicates CSF1 in the formation of high-grade astrocytomas.
Sleeping beauty-mediated somatic mutagenesis implicates CSF1 in the formation of high-grade astrocytomas.
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DOI：
10.1158/0008-5472.can-09-4674
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发表时间：
2010-05-01
期刊：
影响因子：
11.2
通讯作者：
Jenkins RB
中科院分区：
文献类型：
--
作者：
Bender AM;Collier LS;Rodriguez FJ;Tieu C;Larson JD;Halder C;Mahlum E;Kollmeyer TM;Akagi K;Sarkar G;Largaespada DA;Jenkins RB
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 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 RT-PCR, we documented increased Csf1 RNAs in tumor versus adjacent normal tissue, with 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.
