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Tumor Biology

Abstract LB-132: Adult lineage-restricted CNS progenitors specify distinct glioblastoma subtypes

Sheila R. Alcantara Llaguno, Zilai Wang, Daochun Sun, Jian Chen, Jing Xu, Euiseok Kim, Kimmo Hatanpaa, Jack Raisanen, Dennis Burns, Jane Johnson and Luis F. Parada
Sheila R. Alcantara Llaguno
UT Southwestern Medical Ctr., Dallas, TX.
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Zilai Wang
UT Southwestern Medical Ctr., Dallas, TX.
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Daochun Sun
UT Southwestern Medical Ctr., Dallas, TX.
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Jian Chen
UT Southwestern Medical Ctr., Dallas, TX.
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Jing Xu
UT Southwestern Medical Ctr., Dallas, TX.
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Euiseok Kim
UT Southwestern Medical Ctr., Dallas, TX.
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Kimmo Hatanpaa
UT Southwestern Medical Ctr., Dallas, TX.
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Jack Raisanen
UT Southwestern Medical Ctr., Dallas, TX.
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Dennis Burns
UT Southwestern Medical Ctr., Dallas, TX.
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Jane Johnson
UT Southwestern Medical Ctr., Dallas, TX.
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Luis F. Parada
UT Southwestern Medical Ctr., Dallas, TX.
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DOI: 10.1158/1538-7445.AM2015-LB-132 Published August 2015
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Proceedings: AACR 106th Annual Meeting 2015; April 18-22, 2015; Philadelphia, PA

Abstract

A central question in glioblastoma multiforme (GBM) research is the hierarchy of tumor-initiating cells, and its contribution to the malignant phenotype and genomic make-up of GBM. We examine the potential of adult lineage restricted central nervous system (CNS) progenitors to form malignant gliomas. We show that targeting of Nf1,p53 and Pten mutations in adult CNS progenitors but not stem cells gives rise to fully penetrant GBM. We identify two phenotypically and molecularly distinct GBM subtypes that arise from different adult progenitor lineages. Using multiple inducible cre transgenic lines, we demonstrate that murine GBMs are molecularly separable based on the cell of origin. The oligodendrocyte progenitor cell-derived murine tumors have parallels with a subset of human high-grade gliomas with oligodendrocytic component, tumors that have been ascribed better prognosis compared to classic malignant astrocytomas. These studies indicate that two independent sources of GBM-initiating adult progenitors are susceptible to identical mutations and point to the cell of origin as a major determinant of GBM subtype.

Citation Format: Sheila R. Alcantara Llaguno, Zilai Wang, Daochun Sun, Jian Chen, Jing Xu, Euiseok Kim, Kimmo Hatanpaa, Jack Raisanen, Dennis Burns, Jane Johnson, Luis F. Parada. Adult lineage-restricted CNS progenitors specify distinct glioblastoma subtypes. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr LB-132. doi:10.1158/1538-7445.AM2015-LB-132

  • ©2015 American Association for Cancer Research.
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Cancer Research: 75 (15 Supplement)
August 2015
Volume 75, Issue 15 Supplement
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Abstract LB-132: Adult lineage-restricted CNS progenitors specify distinct glioblastoma subtypes
Sheila R. Alcantara Llaguno, Zilai Wang, Daochun Sun, Jian Chen, Jing Xu, Euiseok Kim, Kimmo Hatanpaa, Jack Raisanen, Dennis Burns, Jane Johnson and Luis F. Parada
Cancer Res August 1 2015 (75) (15 Supplement) LB-132; DOI: 10.1158/1538-7445.AM2015-LB-132

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Abstract LB-132: Adult lineage-restricted CNS progenitors specify distinct glioblastoma subtypes
Sheila R. Alcantara Llaguno, Zilai Wang, Daochun Sun, Jian Chen, Jing Xu, Euiseok Kim, Kimmo Hatanpaa, Jack Raisanen, Dennis Burns, Jane Johnson and Luis F. Parada
Cancer Res August 1 2015 (75) (15 Supplement) LB-132; DOI: 10.1158/1538-7445.AM2015-LB-132
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Cancer Research Online ISSN: 1538-7445
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