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bmi1 and p16 in glioma

M K Sibin, Dhananjaya I Bhat, K V L Narasingarao, Ch Lavanya, G K Chetan
Human high-grade glioma is heterogeneous in nature based on pathological and genetic profiling. Various tumour suppressor gene alterations are considered as prognostic markers in high-grade glioma. Gene expression of CDKN2A (p16) is used in various cancers as a prognostic biomarker along with methylation and deletion status of this gene. Expression levels of p16 mRNA were not studied as a biomarker in gliomas before. In this study, we have performed mRNA quantification analysis on 48 high-grade glioma tissues and checked for a possible prognostic role...
September 2015: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
Leomar Y Ballester, Zengfeng Wang, Shaefali Shandilya, Markku Miettinen, Peter C Burger, Charles G Eberhart, Fausto J Rodriguez, Eric Raabe, Javad Nazarian, Katherine Warren, Martha M Quezado
Tumors of the central nervous system are the second most common malignancy in children. In particular, diffuse intrinsic pontine gliomas (DIPGs) are aggressive tumors with poor prognosis and account for 10% to 25% of pediatric brain tumors. The majority of DIPGs are astrocytic, infiltrative, and localized to the pons. Studies have shown median survival times of less than a year, with 90% of children dying within 2 years. We built multitissue arrays with 24 postmortem DIPG samples and analyzed the morphology and expression of several proteins (p53, EGFR, GFAP, MIB1, BMI1, β-catenin, p16, Nanog, Nestin, OCT4, OLIG2, SOX2) with the goal of identifying potential treatment targets and improving our understanding of the biology of these tumors...
September 2013: American Journal of Surgical Pathology
Gaetano Gargiulo, Matteo Cesaroni, Michela Serresi, Nienke de Vries, Danielle Hulsman, Sophia W Bruggeman, Cesare Lancini, Maarten van Lohuizen
In mouse and human neural progenitor and glioblastoma "stem-like" cells, we identified key targets of the Polycomb-group protein BMI1 by combining ChIP-seq with in vivo RNAi screening. We discovered that Bmi1 is important in the cellular response to the transforming growth factor-β/bone morphogenetic protein (TGF-β/BMP) and endoplasmic reticulum (ER) stress pathways, in part converging on the Atf3 transcriptional repressor. We show that Atf3 is a tumor-suppressor gene inactivated in human glioblastoma multiforme together with Cbx7 and a few other candidates...
May 13, 2013: Cancer Cell
Sophia W M Bruggeman, Danielle Hulsman, Maarten van Lohuizen
BACKGROUND: Neural cells deficient for Polycomb group (PcG) protein Bmi1 are impaired in the formation and differentiation of high grade glioma, an incurable cancer of the brain. It was shown that mechanisms involved in cell adhesion and migration were specifically affected in these tumors. METHODS: Using biochemical and cell biological approaches, we investigated the adhesive capacities of Bmi1;Ink4a/Arf deficient primary neural stem cells (NSCs). RESULTS: Bmi1;Ink4a/Arf deficient NSCs have altered expression of Collagen-related genes, secrete increased amounts of extracellular matrix, and exhibit enhanced cell-matrix binding through the Beta-1 Integrin receptor...
May 2009: Biochimica et Biophysica Acta
Sophia W M Bruggeman, Danielle Hulsman, Ellen Tanger, Tessa Buckle, Marleen Blom, John Zevenhoven, Olaf van Tellingen, Maarten van Lohuizen
The Polycomb group and oncogene Bmi1 is required for the proliferation of various differentiated cells and for the self-renewal of stem cells and leukemic cancer stem cells. Repression of the Ink4a/Arf locus is a well described mechanism through which Bmi1 can exert its proliferative effects. However, we now demonstrate in an orthotopic transplantation model for glioma, a type of cancer harboring cancer stem cells, that Bmi1 is also required for tumor development in an Ink4a/Arf-independent manner. Tumors derived from Bmi1;Ink4a/Arf doubly deficient astrocytes or neural stem cells have a later time of onset and different histological grading...
October 2007: Cancer Cell
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