Abstract
Subsets of high-grade gliomas, including glioblastoma (GBM), are known to utilize the alternative lengthening of telomeres (ALT) pathway for telomere length maintenance. However, the telomere maintenance profile of one subtype of GBM-giant cell GBM-has not been extensively studied. Here, we investigated the prevalence of ALT, as well as ATRX and SMARCAL1 protein loss, in a cohort of classic giant cell GBM and GBM with giant cell features. To determine the presence of ALT, a telomere-specific fluorescence in situ hybridization assay was performed on 15 cases of classic giant cell GBM, 28 additional GBMs found to have giant cell features, and 1 anaplastic astrocytoma with giant cell features. ATRX, SMARCAL1, and IDH1 protein status were assessed in a proportion of cases by immunohistochemistry and were compared to clinical-pathologic and molecular characteristics. In the overall cohort of 44 cases, 19 (43%) showed evidence of ALT. Intriguingly, of the ALT-positive cases, only 9 (47.4%) displayed loss of the ALT suppressor ATRX by immunohistochemistry. Since inactivating mutations in SMARCAL1 have been identified in ATRX wild-type ALT-positive gliomas, we developed an immunohistochemistry assay for SMARCAL1 protein expression usin...Continue Reading
References
Jan 27, 2000·Cell·D Hanahan, R A Weinberg
Apr 12, 2002·The American Journal of Pathology·Alan K MeekerAngelo M De Marzo
Mar 19, 2003·Lancet·V Hakin-SmithJ A Royds
Sep 4, 2003·Proceedings of the National Academy of Sciences of the United States of America·Yutong XueWeidong Wang
Oct 29, 2004·Molecular and Cellular Biology·Anthony J Cesare, Jack D Griffith
Jul 5, 2006·Cancer Research·Yu-Jen ChenJanice A Royds
Apr 1, 2009·Neuro-oncology·Kevin R Kozak, John S Moody
Mar 10, 2010·Cell·Aaron D GoldbergC David Allis
Mar 31, 2010·Nature Reviews. Genetics·Anthony J Cesare, Roger R Reddel
May 28, 2010·Genes & Development·Pascal DranéAli Hamiche
Jun 11, 2010·Journal of Neuropathology and Experimental Neurology·Kerrie L McDonaldJanice A Royds
Jul 24, 2010·Proceedings of the National Academy of Sciences of the United States of America·Peter W LewisC David Allis
Mar 23, 2011·Stem Cells·David C SilvestreFrançois D Boussin
Jul 2, 2011·Science·Christopher M HeaphyAlan K Meeker
Sep 6, 2011·The American Journal of Pathology·Christopher M HeaphyAlan K Meeker
Aug 8, 2012·Oncotarget·Yuchen JiaoHai Yan
Aug 30, 2012·Brain Pathology·Doreen N NguyenFausto J Rodriguez
Mar 27, 2013·Proceedings of the National Academy of Sciences of the United States of America·Patrick J KillelaHai Yan
Jun 15, 2013·Modern Pathology : an Official Journal of the United States and Canadian Academy of Pathology, Inc·Malak AbedalthagafiArie Perry
Apr 8, 2014·Nature Genetics·Gang WuSuzanne J Baker
Jul 20, 2014·Journal of Clinical Neuroscience : Official Journal of the Neurosurgical Society of Australasia·Taemin OhAndrew T Parsa
May 23, 2015·Oncotarget·Christine E NapierRoger R Reddel
Jul 7, 2015·Nature Communications·David ClynesRichard J Gibbons
Oct 8, 2015·Brain Pathology·Ji Eun OhHiroko Ohgaki
Oct 21, 2015·Acta Neuropathologica·Andrey KorshunovDavid T W Jones
Nov 19, 2015·Proceedings of the National Academy of Sciences of the United States of America·Lisa A PooleDavid Cortez
Feb 3, 2016·Cell Reports·Kelli E CoxRachel Litman Flynn
May 10, 2016·Acta Neuropathologica·David N LouisDavid W Ellison
Oct 22, 2016·Acta Neuropathologica·Fausto J RodriguezChristopher M Heaphy
May 29, 2018·Nature Communications·Bill H DiplasHai Yan
Jun 23, 2018·JAMA Oncology·Quinn T OstromJill S Barnholtz-Sloan
Dec 12, 2018·Nature Medicine·Fulvio D'AngeloAntonio Iavarone
Apr 23, 2019·World Neurosurgery·Michael C JinErqi L Pollom
Aug 30, 2019·Acta Neuropathologica Communications·Fausto J RodriguezChristopher M Heaphy