Journal Article
. 2007 Apr; 13(7):2038-45.
doi: 10.1158/1078-0432.CCR-06-2149.

Loss of the mismatch repair protein MSH6 in human glioblastomas is associated with tumor progression during temozolomide treatment

Daniel P Cahill 1 Kymberly K Levine  Rebecca A Betensky  Patrick J Codd  Candice A Romany  Linsey B Reavie  Tracy T Batchelor  P Andrew Futreal  Michael R Stratton  William T Curry  A John Iafrate  David N Louis  
Affiliations
  • PMID: 17404084
  •     36 References
  •     181 citations

Abstract

Purpose: Glioblastomas are treated by surgical resection followed by radiotherapy [X-ray therapy (XRT)] and the alkylating chemotherapeutic agent temozolomide. Recently, inactivating mutations in the mismatch repair gene MSH6 were identified in two glioblastomas recurrent post-temozolomide. Because mismatch repair pathway inactivation is a known mediator of alkylator resistance in vitro, these findings suggested that MSH6 inactivation was causally linked to these two recurrences. However, the extent of involvement of MSH6 in glioblastoma is unknown. We sought to determine the overall frequency and clinical relevance of MSH6 alterations in glioblastomas.

Experimental Design: The MSH6 gene was sequenced in 54 glioblastomas. MSH6 and O(6)-methylguanine methyltransferase (MGMT) immunohistochemistry was systematically scored in a panel of 46 clinically well-characterized glioblastomas, and the corresponding patient response to treatment evaluated.

Results: MSH6 mutation was not observed in any pretreatment glioblastoma (0 of 40), whereas 3 of 14 recurrent cases had somatic mutations (P = 0.015). MSH6 protein expression was detected in all pretreatment (17 of 17) cases examined but, notably, expression was lost in 7 of 17 (41%) recurrences from matched post-XRT + temozolomide cases (P = 0.016). Loss of MSH6 was not associated with O(6)-methylguanine methyltransferase status. Measurements of in vivo tumor growth using three-dimensional reconstructed magnetic resonance imaging showed that MSH6-negative glioblastomas had a markedly increased rate of growth while under temozolomide treatment (3.17 versus 0.04 cc/mo for MSH6-positive tumors; P = 0.020).

Conclusions: Loss of MSH6 occurs in a subset of post-XRT + temozolomide glioblastoma recurrences and is associated with tumor progression during temozolomide treatment, mirroring the alkylator resistance conferred by MSH6 inactivation in vitro. MSH6 deficiency may therefore contribute to the emergence of recurrent glioblastomas during temozolomide treatment.

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Nat Rev Cancer, 2015 Jan 09; 14(12). PMID: 25568919    Free PMC article.
Highly Cited. Review.
Advances and challenges in the molecular biology and treatment of glioblastoma-is there any hope for the future?
Ignacio Veliz, Yong Loo, +3 authors, Rafael Rosell.
Ann Transl Med, 2015 Feb 24; 3(1). PMID: 25705639    Free PMC article.
Review.
Evolution of DNA repair defects during malignant progression of low-grade gliomas after temozolomide treatment.
Hinke F van Thuijl, Tali Mazor, +21 authors, Joseph F Costello.
Acta Neuropathol, 2015 Mar 01; 129(4). PMID: 25724300    Free PMC article.
Highly Cited.
A transcriptomic signature mediated by HOXA9 promotes human glioblastoma initiation, aggressiveness and resistance to temozolomide.
Marta Pojo, Céline S Gonçalves, +12 authors, Bruno M Costa.
Oncotarget, 2015 Mar 13; 6(10). PMID: 25762636    Free PMC article.
Recurrence of glioblastoma after radio-chemotherapy is associated with an angiogenic switch to the CXCL12-CXCR4 pathway.
Emeline Tabouret, Aurelie Tchoghandjian, +9 authors, Olivier Chinot.
Oncotarget, 2015 Apr 11; 6(13). PMID: 25860928    Free PMC article.
Motivating the additional use of external validity: examining transportability in a model of glioblastoma multiforme.
Kyle W Singleton, William Speier, Alex A T Bui, William Hsu.
AMIA Annu Symp Proc, 2014 Jan 01; 2014. PMID: 25954466    Free PMC article.
Minor Changes in Expression of the Mismatch Repair Protein MSH2 Exert a Major Impact on Glioblastoma Response to Temozolomide.
José L McFaline-Figueroa, Christian J Braun, +12 authors, Leona D Samson.
Cancer Res, 2015 May 31; 75(15). PMID: 26025730    Free PMC article.
Advances in the treatment of newly diagnosed glioblastoma.
Brett J Theeler, Mark R Gilbert.
BMC Med, 2015 Dec 10; 13. PMID: 26646075    Free PMC article.
Review.
Mismatch repair defects and Lynch syndrome: The role of the basic scientist in the battle against cancer.
Christopher D Heinen.
DNA Repair (Amst), 2015 Dec 30; 38. PMID: 26710976    Free PMC article.
Review.
Intratumoral heterogeneity identified at the epigenetic, genetic and transcriptional level in glioblastoma.
Nicole R Parker, Amanda L Hudson, +9 authors, Viive M Howell.
Sci Rep, 2016 Mar 05; 6. PMID: 26940435    Free PMC article.
Highly Cited.
NOTCH blockade combined with radiation therapy and temozolomide prolongs survival of orthotopic glioblastoma.
Sanaz Yahyanejad, Henry King, +12 authors, Marc Vooijs.
Oncotarget, 2016 May 18; 7(27). PMID: 27183910    Free PMC article.
Clonal evolution of glioblastoma under therapy.
Jiguang Wang, Emanuela Cazzato, +17 authors, Raul Rabadan.
Nat Genet, 2016 Jun 09; 48(7). PMID: 27270107    Free PMC article.
Highly Cited.
Augmented HR Repair Mediates Acquired Temozolomide Resistance in Glioblastoma.
Carlos Rodrigo Gil Del Alcazar, Pavlina Krasimirova Todorova, +2 authors, Sandeep Burma.
Mol Cancer Res, 2016 Jul 01; 14(10). PMID: 27358111    Free PMC article.
Pembrolizumab: first experience with recurrent primary central nervous system (CNS) tumors.
Deborah T Blumenthal, Michal Yalon, +6 authors, Felix Bokstein.
J Neurooncol, 2016 Jul 06; 129(3). PMID: 27377654
Association of MSH6 mutation with glioma susceptibility, drug resistance and progression.
Chaoran Xie, Hansong Sheng, +3 authors, Xuesheng Zheng.
Mol Clin Oncol, 2016 Jul 23; 5(2). PMID: 27446556    Free PMC article.
How effective is temozolomide for treating pituitary tumours and when should it be used?
Carmel Halevy, Benjamin C Whitelaw.
Pituitary, 2016 Sep 02; 20(2). PMID: 27581836
Review.
Immunogenomics of Hypermutated Glioblastoma: A Patient with Germline POLE Deficiency Treated with Checkpoint Blockade Immunotherapy.
Tanner M Johanns, Christopher A Miller, +10 authors, Gavin P Dunn.
Cancer Discov, 2016 Nov 04; 6(11). PMID: 27683556    Free PMC article.
Highly Cited.
Metformin treatment reduces temozolomide resistance of glioblastoma cells.
Seung Ho Yang, Shenglan Li, +4 authors, Ying Liu.
Oncotarget, 2016 Oct 30; 7(48). PMID: 27791206    Free PMC article.
Endogenous Neoantigen-Specific CD8 T Cells Identified in Two Glioblastoma Models Using a Cancer Immunogenomics Approach.
Tanner M Johanns, Jeffrey P Ward, +9 authors, Gavin P Dunn.
Cancer Immunol Res, 2016 Nov 02; 4(12). PMID: 27799140    Free PMC article.
The Major Replicative Histone Chaperone CAF-1 Suppresses the Activity of the DNA Mismatch Repair System in the Cytotoxic Response to a DNA-methylating Agent.
Lyudmila Y Kadyrova, Basanta K Dahal, Farid A Kadyrov.
J Biol Chem, 2016 Nov 23; 291(53). PMID: 27872185    Free PMC article.
Drug-Repositioning Screens Identify Triamterene as a Selective Drug for the Treatment of DNA Mismatch Repair Deficient Cells.
Delphine Guillotin, Philip Austin, +6 authors, Sarah A Martin.
Clin Cancer Res, 2016 Dec 04; 23(11). PMID: 27913567    Free PMC article.
Longitudinal analysis of treatment-induced genomic alterations in gliomas.
E Zeynep Erson-Omay, Octavian Henegariu, +18 authors, Murat Günel.
Genome Med, 2017 Feb 06; 9(1). PMID: 28153049    Free PMC article.
1,2:5,6-dianhydrogalactitol inhibits human glioma cell growth in vivo and in vitro by arresting the cell cycle at G2/M phase.
Chun Peng, Xin-Ming Qi, Ling-Ling Miao, Jin Ren.
Acta Pharmacol Sin, 2017 Feb 22; 38(4). PMID: 28216618    Free PMC article.
The Role of Immune Checkpoint Inhibition in the Treatment of Brain Tumors.
Andrew S Luksik, Russell Maxwell, Tomas Garzon-Muvdi, Michael Lim.
Neurotherapeutics, 2017 Mar 05; 14(4). PMID: 28258545    Free PMC article.
Review.
Treatment-Induced Mutagenesis and Selective Pressures Sculpt Cancer Evolution.
Subramanian Venkatesan, Charles Swanton, Barry S Taylor, Joseph F Costello.
Cold Spring Harb Perspect Med, 2017 Mar 16; 7(8). PMID: 28289245    Free PMC article.
Review.
Immune checkpoint inhibition and its relationship with hypermutation phenoytype as a potential treatment for Glioblastoma.
Manohan Sinnadurai, Kerrie L McDonald.
J Neurooncol, 2017 Mar 16; 132(3). PMID: 28293764
Review.
Immune Checkpoint Inhibitors in Gliomas.
Aaron C Tan, Amy B Heimberger, Mustafa Khasraw.
Curr Oncol Rep, 2017 Mar 18; 19(4). PMID: 28303490
Review.
Mutational burden, immune checkpoint expression, and mismatch repair in glioma: implications for immune checkpoint immunotherapy.
Tiffany R Hodges, Martina Ott, +9 authors, Amy B Heimberger.
Neuro Oncol, 2017 Apr 04; 19(8). PMID: 28371827    Free PMC article.
Highly Cited.
Is more better? The impact of extended adjuvant temozolomide in newly diagnosed glioblastoma: a secondary analysis of EORTC and NRG Oncology/RTOG.
Deborah T Blumenthal, Thierry Gorlia, +18 authors, Roger Stupp.
Neuro Oncol, 2017 Apr 04; 19(8). PMID: 28371907    Free PMC article.
Applied Cancer Immunogenomics: Leveraging Neoantigen Discovery in Glioblastoma.
Tanner M Johanns, Gavin P Dunn.
Cancer J, 2017 Apr 15; 23(2). PMID: 28410300    Free PMC article.
Review.
Chemotherapeutic Drugs: DNA Damage and Repair in Glioblastoma.
Laura Annovazzi, Marta Mellai, Davide Schiffer.
Cancers (Basel), 2017 Jun 08; 9(6). PMID: 28587121    Free PMC article.
Review.
Characterization of gliomas: from morphology to molecules.
Sean P Ferris, Jeffrey W Hofmann, David A Solomon, Arie Perry.
Virchows Arch, 2017 Jul 05; 471(2). PMID: 28674742
Review.
Acquired temozolomide resistance in human glioblastoma cell line U251 is caused by mismatch repair deficiency and can be overcome by lomustine.
J Stritzelberger, L Distel, +2 authors, F Putz.
Clin Transl Oncol, 2017 Aug 22; 20(4). PMID: 28825189
Targeting Neoantigens in Glioblastoma: An Overview of Cancer Immunogenomics and Translational Implications.
Tanner M Johanns, Jay A Bowman-Kirigin, Connor Liu, Gavin P Dunn.
Neurosurgery, 2017 Sep 14; 64(CN_suppl_1). PMID: 28899059    Free PMC article.
MGMT and MSH6 immunoexpression for functioning pituitary macroadenomas.
Alexander S G Micko, Adelheid Wöhrer, +4 authors, Stefan Wolfsberger.
Pituitary, 2017 Sep 14; 20(6). PMID: 28900805    Free PMC article.
Restricted Delivery of Talazoparib Across the Blood-Brain Barrier Limits the Sensitizing Effects of PARP Inhibition on Temozolomide Therapy in Glioblastoma.
Sani H Kizilbash, Shiv K Gupta, +13 authors, Jann N Sarkaria.
Mol Cancer Ther, 2017 Sep 28; 16(12). PMID: 28947502    Free PMC article.
Persistence of DNA adducts, hypermutation and acquisition of cellular resistance to alkylating agents in glioblastoma.
R J Head, M F Fay, +3 authors, J H Martin.
Cancer Biol Ther, 2017 Oct 12; 18(12). PMID: 29020502    Free PMC article.
Review.
Inactivation of DNA repair triggers neoantigen generation and impairs tumour growth.
Giovanni Germano, Simona Lamba, +23 authors, Alberto Bardelli.
Nature, 2017 Dec 01; 552(7683). PMID: 29186113
Highly Cited.
Biological and therapeutic implications of multisector sequencing in newly diagnosed glioblastoma.
Tatenda Mahlokozera, Ananth K Vellimana, +10 authors, Albert H Kim.
Neuro Oncol, 2017 Dec 16; 20(4). PMID: 29244145    Free PMC article.
Treatment of aggressive prolactinoma with temozolomide: A case report and review of literature up to date.
Cheng Chen, Senlin Yin, +4 authors, Shu Jiang.
Medicine (Baltimore), 2018 Feb 01; 96(47). PMID: 29381964    Free PMC article.
Autophagy activation promotes bevacizumab resistance in glioblastoma by suppressing Akt/mTOR signaling pathway.
He Huang, Jian Song, +2 authors, Guozheng Xu.
Oncol Lett, 2018 Feb 13; 15(2). PMID: 29434840    Free PMC article.
NEO212 Inhibits Migration and Invasion of Glioma Stem Cells.
Nagore I Marín-Ramos, Thu Zan Thein, +5 authors, Florence M Hofman.
Mol Cancer Ther, 2018 Feb 15; 17(3). PMID: 29440289    Free PMC article.
MSH6 haploinsufficiency at relapse contributes to the development of thiopurine resistance in pediatric B-lymphoblastic leukemia.
Nikki A Evensen, P Pallavi Madhusoodhan, +11 authors, William L Carroll.
Haematologica, 2018 Feb 17; 103(5). PMID: 29449434    Free PMC article.
Temozolomide-associated hypermutation in gliomas.
Serah Choi, Yao Yu, +3 authors, Joseph F Costello.
Neuro Oncol, 2018 Feb 17; 20(10). PMID: 29452419    Free PMC article.
Highly Cited. Review.
Quo Vadis-Do Immunotherapies Have a Role in Glioblastoma?
Sylvia C Kurz, Patrick Y Wen.
Curr Treat Options Neurol, 2018 Apr 19; 20(5). PMID: 29666934
Review.
The possibility of cancer immune editing in gliomas. A critical review.
Víctor A Arrieta, Bernardo Cacho-Díaz, +3 authors, Adam M Sonabend.
Oncoimmunology, 2018 Jun 15; 7(7). PMID: 29900059    Free PMC article.
Review.
Temozolomide and Pituitary Tumors: Current Understanding, Unresolved Issues, and Future Directions.
Luis V Syro, Fabio Rotondo, +3 authors, Kalman Kovacs.
Front Endocrinol (Lausanne), 2018 Jul 03; 9. PMID: 29963012    Free PMC article.
Review.
Cell surface vimentin-targeted monoclonal antibody 86C increases sensitivity to temozolomide in glioma stem cells.
Hyangsoon Noh, Qingnan Zhao, +6 authors, Shulin Li.
Cancer Lett, 2018 Jul 12; 433. PMID: 29991446    Free PMC article.
ABT-888 restores sensitivity in temozolomide resistant glioma cells and xenografts.
Alice L Yuan, Christian B Ricks, +23 authors, Michael D Blough.
PLoS One, 2018 Aug 29; 13(8). PMID: 30153289    Free PMC article.
[Advances on Recognizing and Managing Tumor Heterogeneity].
Rui Zhong, Hui Li, +2 authors, Ying Cheng.
Zhongguo Fei Ai Za Zhi, 2018 Sep 12; 21(9). PMID: 30201072    Free PMC article.
Review.
PLK1 Inhibition Targets Myc-Activated Malignant Glioma Cells Irrespective of Mismatch Repair Deficiency-Mediated Acquired Resistance to Temozolomide.
Fumi Higuchi, Alexandria L Fink, +4 authors, Hiroaki Wakimoto.
Mol Cancer Ther, 2018 Sep 16; 17(12). PMID: 30217967    Free PMC article.
Glioblastoma Chemoresistance: The Double Play by Microenvironment and Blood-Brain Barrier.
Martina Da Ros, Veronica De Gregorio, +5 authors, Iacopo Sardi.
Int J Mol Sci, 2018 Sep 27; 19(10). PMID: 30248992    Free PMC article.
Review.
Rare Stochastic Expression of O6-Methylguanine- DNA Methyltransferase (MGMT) in MGMT-Negative Melanoma Cells Determines Immediate Emergence of Drug-Resistant Populations upon Treatment with Temozolomide In Vitro and In Vivo.
Thomas C Chen, Nymph Chan, +3 authors, Axel H Schönthal.
Cancers (Basel), 2018 Oct 03; 10(10). PMID: 30274152    Free PMC article.
Radiation Drives the Evolution of Orthotopic Xenografts Initiated from Glioblastoma Stem-like Cells.
Joseph H McAbee, Barbara H Rath, +5 authors, Philip J Tofilon.
Cancer Res, 2019 Oct 17; 79(23). PMID: 31615806    Free PMC article.
Checkpoint inhibitor failure in hypermutated and mismatch repair-mutated recurrent high-grade gliomas.
Haroon Ahmad, Camilo E Fadul, David Schiff, Benjamin Purow.
Neurooncol Pract, 2019 Dec 14; 6(6). PMID: 31832212    Free PMC article.
Genomic landscapes by multiregion sequencing combined with circulation tumor DNA detection contribute to molecular diagnosis in glioblastomas.
Chao Yang, Yanli Tan, +8 authors, Chunsheng Kang.
Aging (Albany NY), 2019 Dec 12; 11(23). PMID: 31822636    Free PMC article.
A novel DNA damage response signature of IDH-mutant grade II and grade III astrocytoma at transcriptional level.
Qi Liu, Kuanyu Wang, +4 authors, Pei Yang.
J Cancer Res Clin Oncol, 2020 Feb 16; 146(3). PMID: 32060643
Marked Response of a Hypermutated ACTH-Secreting Pituitary Carcinoma to Ipilimumab and Nivolumab.
Andrew L Lin, Philip Jonsson, +11 authors, Eliza B Geer.
J Clin Endocrinol Metab, 2018 Aug 08; 103(10). PMID: 30085142    Free PMC article.
Hypermutagenesis in untreated adult gliomas due to inherited mismatch mutations.
Jason K Sa, Seung Won Choi, +9 authors, Do-Hyun Nam.
Int J Cancer, 2018 Dec 12; 144(12). PMID: 30536544    Free PMC article.
Sequencing and curation strategies for identifying candidate glioblastoma treatments.
Mayu O Frank, Takahiko Koyama, +46 authors, Robert B Darnell.
BMC Med Genomics, 2019 Apr 27; 12(1). PMID: 31023376    Free PMC article.
Programmed Death Ligand 1 Is a Negative Prognostic Marker in Recurrent Isocitrate Dehydrogenase-Wildtype Glioblastoma.
Drew Pratt, Gifty Dominah, +12 authors, Edjah K Nduom.
Neurosurgery, 2018 Jul 17; 85(2). PMID: 30011045    Free PMC article.
Aberrant Transcriptional Regulation of Super-enhancers by RET Finger Protein-histone Deacetylase 1 Complex in Glioblastoma: Chemoresistance to Temozolomide.
Atsushi Natsume, Masaki Hirano, +2 authors, Toshihiko Wakabayashi.
Neurol Med Chir (Tokyo), 2019 Jun 11; 59(8). PMID: 31178471    Free PMC article.
Review.
Toward a standard pathological and molecular characterization of recurrent glioma in adults: a Response Assessment in Neuro-Oncology effort.
Ali S Haider, Martin van den Bent, +5 authors, Jason T Huse.
Neuro Oncol, 2019 Dec 18; 22(4). PMID: 31844891    Free PMC article.
Review.
Restoration of Temozolomide Sensitivity by PARP Inhibitors in Mismatch Repair Deficient Glioblastoma is Independent of Base Excision Repair.
Fumi Higuchi, Hiroaki Nagashima, +3 authors, Daniel P Cahill.
Clin Cancer Res, 2020 Jan 05; 26(7). PMID: 31900275    Free PMC article.
Epigenetic preconditioning with decitabine sensitizes glioblastoma to temozolomide via induction of MLH1.
Matthew Gallitto, Rossana Cheng He, +8 authors, Raymund L Yong.
J Neurooncol, 2020 Mar 21; 147(3). PMID: 32193690    Free PMC article.
Constitutional mismatch repair deficiency-associated brain tumors: report from the European C4CMMRD consortium.
Léa Guerrini-Rousseau, Pascale Varlet, +17 authors, Laurence Brugières.
Neurooncol Adv, 2020 Jul 10; 1(1). PMID: 32642664    Free PMC article.
Progress in Neoantigen Targeted Cancer Immunotherapies.
Xue-Jiao Han, Xue-Lei Ma, +3 authors, Xia-Wei Wei.
Front Cell Dev Biol, 2020 Aug 28; 8. PMID: 32850843    Free PMC article.
Review.
Durable Near-Complete Response to Olaparib Plus Temozolomide and Radiation in a Patient With ATM-Mutated Glioblastoma and MSH6-Deficient Lynch Syndrome.
Danielle M File, Katherine P Morgan, Simon Khagi.
JCO Precis Oncol, 2020 Sep 15; 4. PMID: 32923878    Free PMC article.
Mismatch repair deficiency in high-grade meningioma: a rare but recurrent event associated with dramatic immune activation and clinical response to PD-1 blockade.
Ian F Dunn, Ziming Du, +16 authors, David A Reardon.
JCO Precis Oncol, 2019 Feb 26; 2018. PMID: 30801050    Free PMC article.
Molecular Neuropathology in Practice: Clinical Profiling and Integrative Analysis of Molecular Alterations in Glioblastoma.
MacLean P Nasrallah, Zev A Binder, +11 authors, Jennifer J D Morrissette.
Acad Pathol, 2019 Jun 18; 6. PMID: 31206012    Free PMC article.
Mismatch-Repair Protein Expression in High-Grade Gliomas: A Large Retrospective Multicenter Study.
Mario Caccese, Tamara Ius, +10 authors, Giuseppe Lombardi.
Int J Mol Sci, 2020 Sep 18; 21(18). PMID: 32937743    Free PMC article.
Poly(ADP-ribose) Glycohydrolase Inhibition Sequesters NAD+ to Potentiate the Metabolic Lethality of Alkylating Chemotherapy in IDH-Mutant Tumor Cells.
Hiroaki Nagashima, Christine K Lee, +7 authors, Daniel P Cahill.
Cancer Discov, 2020 Jul 02; 10(11). PMID: 32606138    Free PMC article.
PD-1 Inhibitors: Do they have a Future in the Treatment of Glioblastoma?
Mustafa Khasraw, David A Reardon, Michael Weller, John H Sampson.
Clin Cancer Res, 2020 Jun 13; 26(20). PMID: 32527943    Free PMC article.
Review.
Emerging immunotherapies for malignant glioma: from immunogenomics to cell therapy.
Gavin P Dunn, Timothy F Cloughesy, +3 authors, Adam M Sonabend.
Neuro Oncol, 2020 Jul 03; 22(10). PMID: 32615600    Free PMC article.
Review.
Case Report: A Case of Pituitary Carcinoma Treated With Sequential Dual Immunotherapy and Vascular Endothelial Growth Factor Inhibition Therapy.
Lydia S Lamb, Hao-Wen Sim, Ann I McCormack.
Front Endocrinol (Lausanne), 2020 Dec 15; 11. PMID: 33312158    Free PMC article.
The Molecular and Microenvironmental Landscape of Glioblastomas: Implications for the Novel Treatment Choices.
Federica Di Cintio, Michele Dal Bo, +3 authors, Giuseppe Toffoli.
Front Neurosci, 2020 Dec 17; 14. PMID: 33324155    Free PMC article.
Review.
Targeting the Ubiquitin System in Glioblastoma.
Nico Scholz, Kathreena M Kurian, Florian A Siebzehnrubl, Julien D F Licchesi.
Front Oncol, 2020 Dec 17; 10. PMID: 33324551    Free PMC article.
Review.
Frequent loss of mutation-specific mismatch repair protein expression in nonneoplastic endometrium of Lynch syndrome patients.
Serena Wong, Pei Hui, Natalia Buza.
Mod Pathol, 2020 Jan 15; 33(6). PMID: 31932681
The Progress of Immunotherapy in Refractory Pituitary Adenomas and Pituitary Carcinomas.
Congxin Dai, Siyu Liang, Bowen Sun, Jun Kang.
Front Endocrinol (Lausanne), 2020 Dec 29; 11. PMID: 33362722    Free PMC article.
Review.
Primary mismatch repair deficient IDH-mutant astrocytoma (PMMRDIA) is a distinct type with a poor prognosis.
Abigail K Suwala, Damian Stichel, +32 authors, David E Reuss.
Acta Neuropathol, 2020 Nov 21; 141(1). PMID: 33216206    Free PMC article.
Molecular Mechanisms of Treatment Resistance in Glioblastoma.
Alexander Ou, W K Alfred Yung, Nazanin Majd.
Int J Mol Sci, 2021 Jan 06; 22(1). PMID: 33396284    Free PMC article.
Review.
Genome Medicine for Brain Tumors: Current Status and Future Perspectives.
Akitake Mukasa.
Neurol Med Chir (Tokyo), 2020 Oct 20; 60(11). PMID: 33071276    Free PMC article.
Review.
Management of gliomas in patients with Lynch syndrome.
Iyad Alnahhas, Appaji Rayi, +2 authors, Vinay Puduvalli.
Neuro Oncol, 2020 Oct 16; 23(1). PMID: 33059358    Free PMC article.
Hypermutated phenotype in gliosarcoma of the spinal cord.
Christopher S Hong, Gregory A Kuzmik, +6 authors, E Zeynep Erson-Omay.
NPJ Precis Oncol, 2021 Feb 14; 5(1). PMID: 33580181    Free PMC article.
Neuro-Oncology Practice Clinical Debate: Early treatment or observation for patients with newly diagnosed oligodendroglioma and small-volume residual disease.
Shannon E Fogh, Lauren Boreta, +3 authors, Sylvia C Kurz.
Neurooncol Pract, 2021 Mar 06; 8(1). PMID: 33664965    Free PMC article.
Review.
Forkhead box protein O3a promotes glioma cell resistance to temozolomide by regulating matrix metallopeptidase and β-catenin.
Datong Sun, Shenghui Yang, +5 authors, Ke Xu.
Oncol Lett, 2021 Mar 12; 21(4). PMID: 33692860    Free PMC article.
The Many Facets of Therapy Resistance and Tumor Recurrence in Glioblastoma.
Anshika Goenka, Deanna Tiek, +3 authors, Shi-Yuan Cheng.
Cells, 2021 Mar 07; 10(3). PMID: 33668200    Free PMC article.
Review.
Mechanisms and therapeutic implications of hypermutation in gliomas.
Mehdi Touat, Yvonne Y Li, +75 authors, Keith L Ligon.
Nature, 2020 Apr 24; 580(7804). PMID: 32322066    Free PMC article.
Incidence, clinicopathologic, and genetic characteristics of mismatch repair gene-mutated glioblastomas.
Yoon Ah Cho, Deokgeun Kim, +2 authors, Yeon-Lim Suh.
J Neurooncol, 2021 Apr 18; 153(1). PMID: 33864561
Loss of the abasic site sensor HMCES is synthetic lethal with the activity of the APOBEC3A cytosine deaminase in cancer cells.
Josep Biayna, Isabel Garcia-Cao, +5 authors, Travis H Stracker.
PLoS Biol, 2021 Apr 01; 19(3). PMID: 33788831    Free PMC article.
Downregulation of both mismatch repair and non-homologous end-joining pathways in hypoxic brain tumour cell lines.
Sophie Cowman, Barry Pizer, Violaine Sée.
PeerJ, 2021 May 15; 9. PMID: 33986995    Free PMC article.
DNA damage repair in glioblastoma: current perspectives on its role in tumour progression, treatment resistance and PIKKing potential therapeutic targets.
Mathew Lozinski, Nikola A Bowden, +2 authors, Paul A Tooney.
Cell Oncol (Dordr), 2021 Jun 01; 44(5). PMID: 34057732
Review.
From Laboratory Studies to Clinical Trials: Temozolomide Use in IDH-Mutant Gliomas.
Xueyuan Sun, Sevin Turcan.
Cells, 2021 Jun 03; 10(5). PMID: 34067729    Free PMC article.
Review.
Temozolomide: An Updated Overview of Resistance Mechanisms, Nanotechnology Advances and Clinical Applications.
Raúl Ortiz, Gloria Perazzoli, +4 authors, Consolación Melguizo.
Curr Neuropharmacol, 2020 Jun 27; 19(4). PMID: 32589560    Free PMC article.
Review.
Immunotherapy in Glioblastoma: A Clinical Perspective.
Nicolas Desbaillets, Andreas Felix Hottinger.
Cancers (Basel), 2021 Aug 08; 13(15). PMID: 34359621    Free PMC article.
Review.
Survival Benefit for Individuals With Constitutional Mismatch Repair Deficiency Undergoing Surveillance.
Carol Durno, Ayse Bahar Ercan, +103 authors, Uri Tabori.
J Clin Oncol, 2021 May 05; 39(25). PMID: 33945292    Free PMC article.
Anti-O6-methylguanine-methyltransferase (MGMT) immunohistochemistry in glioblastoma multiforme: observer variability and lack of association with patient survival impede its use as clinical biomarker.
Matthias Preusser, Robert Charles Janzer, +9 authors, Monika Hegi.
Brain Pathol, 2008 Apr 11; 18(4). PMID: 18400046    Free PMC article.
Atypical teratoid rhabdoid tumors (ATRTs): the British Columbia's Children's Hospital's experience, 1986-2006.
Adam J Fleming, Juliette Hukin, +7 authors, Christopher Dunham.
Brain Pathol, 2011 Dec 23; 22(5). PMID: 22188464    Free PMC article.
Whole-exome sequencing revealed mutational profiles of giant cell glioblastomas.
Zhi-Feng Shi, Kay Ka-Wai Li, +7 authors, Ho-Keung Ng.
Brain Pathol, 2019 Mar 13; 29(6). PMID: 30861589    Free PMC article.
Cyclophosphamide enhances the antitumor potency of GITR engagement by increasing oligoclonal cytotoxic T cell fitness.
Daniel Hirschhorn, Allison Betof Warner, +11 authors, Jedd D Wolchok.
JCI Insight, 2021 Oct 23; 6(20). PMID: 34676831    Free PMC article.
Investigation of the relationship between immune checkpoints and mismatch repair deficiency in recurrent and nonrecurrent glioblastoma
Emel Çakır, İsmail Saygın, Mustafa Emre Ercin.
Turk J Med Sci, 2021 Feb 19; 51(4). PMID: 33600097    Free PMC article.
Lomustine and nimustine exert efficient antitumor effects against glioblastoma models with acquired temozolomide resistance.
Shun Yamamuro, Masamichi Takahashi, +12 authors, Arata Tomiyama.
Cancer Sci, 2021 Sep 19; 112(11). PMID: 34536314    Free PMC article.
Impact of Chromatin Dynamics and DNA Repair on Genomic Stability and Treatment Resistance in Pediatric High-Grade Gliomas.
Lia Pinto, Hanane Baidarjad, Natacha Entz-Werlé, Eric Van Dyck.
Cancers (Basel), 2021 Nov 28; 13(22). PMID: 34830833    Free PMC article.
Review.
A Systematic Review and Meta-Analysis on the Number of Adjuvant Temozolomide Cycles in Newly Diagnosed Glioblastoma.
Fahimeh Attarian, Farzad Taghizadeh-Hesary, +4 authors, Danial Fazilat-Panah.
Front Oncol, 2021 Dec 14; 11. PMID: 34900732    Free PMC article.
Systematic Review.
Hippo Pathway in Regulating Drug Resistance of Glioblastoma.
Giacomo Casati, Laura Giunti, +3 authors, Iacopo Sardi.
Int J Mol Sci, 2021 Dec 25; 22(24). PMID: 34948224    Free PMC article.
Review.
Connexin 43 confers chemoresistance through activating PI3K.
Kevin J Pridham, Farah Shah, +14 authors, Zhi Sheng.
Oncogenesis, 2022 Jan 14; 11(1). PMID: 35022385    Free PMC article.
Malignant Progression of an IDH Mutant Brainstem Glioma in Adult.
Kenshi Sano, Ken-Ichiro Matsuda, +3 authors, Yukihiko Sonoda.
NMC Case Rep J, 2022 Jan 27; 8(1). PMID: 35079479    Free PMC article.
Genetic Characteristics of Mismatch Repair-deficient Glioblastoma.
Kei Kawaguchi, Ryohei Otani, +4 authors, Nobusada Shinoura.
NMC Case Rep J, 2022 Jan 27; 8(1). PMID: 35079518    Free PMC article.
Genotoxic therapy and resistance mechanism in gliomas.
Fengchao Lang, Yang Liu, Fu-Ju Chou, Chunzhang Yang.
Pharmacol Ther, 2021 Jun 26; 228. PMID: 34171339    Free PMC article.
Review.
Mismatch repair proteins play a role in ATR activation upon temozolomide treatment in MGMT-methylated glioblastoma.
Sachita Ganesa, Amrita Sule, Ranjini K Sundaram, Ranjit S Bindra.
Sci Rep, 2022 Apr 08; 12(1). PMID: 35388070    Free PMC article.
Temozolomide Followed by Combination With Low-Dose Ipilimumab and Nivolumab in Patients With Microsatellite-Stable, O6-Methylguanine-DNA Methyltransferase-Silenced Metastatic Colorectal Cancer: The MAYA Trial.
Federica Morano, Alessandra Raimondi, +30 authors, Filippo Pietrantonio.
J Clin Oncol, 2022 Mar 09; 40(14). PMID: 35258987    Free PMC article.
Monocentric evaluation of Ki-67 labeling index in combination with a modified RPA score as a prognostic factor for survival in IDH-wildtype glioblastoma patients treated with radiochemotherapy.
R Dumke, C Dumke, +4 authors, S Lautenschläger.
Strahlenther Onkol, 2022 May 26;. PMID: 35612598
Mutational signatures are markers of drug sensitivity of cancer cells.
Jurica Levatić, Marina Salvadores, Francisco Fuster-Tormo, Fran Supek.
Nat Commun, 2022 May 26; 13(1). PMID: 35614096
Congress of neurological surgeons systematic review and evidence-based guidelines update on the role of neuropathology in the management of progressive glioblastoma in adults.
Abigail L Goodman, José E Velázquez Vega, Chad Glenn, Jeffrey J Olson.
J Neurooncol, 2022 Jun 02; 158(2). PMID: 35648306
Review.