In:
Cancer Research, American Association for Cancer Research (AACR), Vol. 72, No. 8_Supplement ( 2012-04-15), p. 1434-1434
Abstract:
Human medulloblastomas are molecularly classified into four major subgroups. Among them, the MYC-subgroup, the most aggressive and the least curable is characterized by amplification or overexpression of the c-MYC gene. While mouse models for the human SHH-subgroup have advanced the development of targeted treatments for this subgroup, the absence of a preclinical model for the MYC-subgroup has severely limited our understanding of its biology and treatment. We have now generated the first mouse model of MYC-subgroup medulloblastoma that faithfully recapitulate the transcriptome, histopathology, and clinical behavior of the human disease. This mouse model was generated by orthotopic transplantation of percoll-purified Myc-transduced cerebellar cells from postnatal day 6-7 Trp53-deficient mice into the cortices or the cerebellum of immunocompromised recipient animals. While & gt;2 x 105 cells from the mouse SHH-tumors are required to induce a tumor, 100 MYC-tumor cells were sufficient, suggesting that most MYC-tumor cells are tumor initiating cells. MYC-tumors can be passaged indefinitely as neurospheres that express markers associated with stem cells, including Prom1, Lgr5, Oct4, Nanog, and Sox2 and induce secondary medulloblastomas with similar characteristics as the primary tumors, after orthotopic transplant into the cortices of recipient mice. This novel medulloblastoma model should significantly advance our efforts to develop new therapeutic modalities and to determine the origin of this deadly childhood cancer. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1434. doi:1538-7445.AM2012-143 4
Type of Medium:
Online Resource
ISSN:
0008-5472
,
1538-7445
DOI:
10.1158/1538-7445.AM2012-1434
Language:
English
Publisher:
American Association for Cancer Research (AACR)
Publication Date:
2012
detail.hit.zdb_id:
2036785-5
detail.hit.zdb_id:
1432-1
detail.hit.zdb_id:
410466-3
