Please wait a minute...
Frontiers of Medicine

ISSN 2095-0217

ISSN 2095-0225(Online)

CN 11-5983/R

Postal Subscription Code 80-967

2018 Impact Factor: 1.847

Front Med    2013, Vol. 7 Issue (2) : 150-156     DOI: 10.1007/s11684-013-0267-1
REVIEW |
Progress on molecular biomarkers and classification of malignant gliomas
Chuanbao Zhang1, Zhaoshi Bao1, Wei Zhang1, Tao Jiang1,2()
1. Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing 100050, China; 2. Beijing Neurosurgical Institute, Beijing 100050, China
Download: PDF(135 KB)   HTML
Export: BibTeX | EndNote | Reference Manager | ProCite | RefWorks
Abstract  

Gliomas are the most common primary intracranial tumors in adults. Anaplastic gliomas (WHO grade III) and glioblastomas (WHO grade IV) represent the major groups of malignant gliomas in the brain. Several diagnostic, predictive, and prognostic biomarkers for malignant gliomas have been reported over the last few decades, and these markers have made great contributions to the accuracy of diagnosis, therapeutic decision making, and prognosis of patients. However, heterogeneity in patient outcomes may still be observed, which highlights the insufficiency of a classification system based purely on histopathology. Great efforts have been made to incorporate new information about the molecular landscape of gliomas into novel classifications that may potentially guide treatment. In this review, we summarize three distinctive biomarkers, three most commonly altered pathways, and three classifications based on microarray data in malignant gliomas.

Keywords malignant glioma      molecular biomarker      IDH1      MGMT      molecular classification     
Corresponding Authors: Jiang Tao,Email:jiangtao369@sohu.com   
Issue Date: 05 June 2013
URL:  
http://academic.hep.com.cn/fmd/EN/10.1007/s11684-013-0267-1     OR     http://academic.hep.com.cn/fmd/EN/Y2013/V7/I2/150
BiomarkersDiagnosticPrognosticPredictive
IDH1 mutation
MGMT promoter methylation
LOH of 1p/19q
Tab.1  Summary of diagnostic, prognostic, and predictive values of three distinct markers
1 Louis DN, Ohgaki H, Wiestler OD, Cavenee WK, Burger PC, Jouvet A, Scheithauer BW, Kleihues P. The 2007 WHO classification of tumours of the central nervous system. Acta Neuropathol 2007; 114(2): 97-109
doi: 10.1007/s00401-007-0243-4 pmid:17618441
2 Jones DT, Gronych J, Lichter P, Witt O, Pfister SM. MAPK pathway activation in pilocytic astrocytoma. Cell Mol Life Sci 2012; 69(11): 1799-1811
doi: 10.1007/s00018-011-0898-9 pmid:22159586
3 Biernat W, Huang H, Yokoo H, Kleihues P, Ohgaki H. Predominant expression of mutant EGFR (EGFRvIII) is rare in primary glioblastomas. Brain Pathol 2004; 14(2): 131-136
doi: 10.1111/j.1750-3639.2004.tb00045.x pmid:15193025
4 Ohgaki H, Kleihues P. Population-based studies on incidence, survival rates, and genetic alterations in astrocytic and oligodendroglial gliomas. J Neuropathol Exp Neurol 2005; 64(6): 479-489
pmid:15977639
5 Van Meir EG, Hadjipanayis CG, Norden AD, Shu HK, Wen PY, Olson JJ. Exciting new advances in neuro-oncology: the avenue to a cure for malignant glioma. CA Cancer J Clin 2010; 60(3): 166-193
doi: 10.3322/caac.20069 pmid:20445000
6 Lawrence YR, Mishra MV, Werner-Wasik M, Andrews DW, Showalter TN, Glass J, Shen X, Symon Z, Dicker AP. Improving prognosis of glioblastoma in the 21st century: who has benefited most? Cancer 2012; 118(17): 4228-4234
pmid:22180310
7 Wang Y, Li S, Chen L, You G, Bao Z, Yan W, Shi Z, Chen Y, Yao K, Zhang W, Kang C, Jiang T. Glioblastoma with an oligodendroglioma component: distinct clinical behavior, genetic alterations, and outcome. Neuro-oncol 2012; 14(4): 518-525
doi: 10.1093/neuonc/nor232 pmid:22326863
8 Geisbrecht BV, Gould SJ. The human PICD gene encodes a cytoplasmic and peroxisomal NADP(+)-dependent isocitrate dehydrogenase. J Biol Chem 1999; 274(43): 30527-30533
doi: 10.1074/jbc.274.43.30527 pmid:10521434
9 Parsons DW, Jones S, Zhang X, Lin JC, Leary RJ, Angenendt P, Mankoo P, Carter H, Siu IM, Gallia GL, Olivi A, McLendon R, Rasheed BA, Keir S, Nikolskaya T, Nikolsky Y, Busam DA, Tekleab H, Diaz LA Jr, Hartigan J, Smith DR, Strausberg RL, Marie SK, Shinjo SM, Yan H, Riggins GJ, Bigner DD, Karchin R, Papadopoulos N, Parmigiani G, Vogelstein B, Velculescu VE, Kinzler KW. An integrated genomic analysis of human glioblastoma multiforme. Science 2008; 321(5897): 1807-1812
doi: 10.1126/science.1164382 pmid:18772396
10 Yan H, Parsons DW, Jin G, McLendon R, Rasheed BA, Yuan W, Kos I, Batinic-Haberle I, Jones S, Riggins GJ, Friedman H, Friedman A, Reardon D, Herndon J, Kinzler KW, Velculescu VE, Vogelstein B, Bigner DD. IDH1 and IDH2 mutations in gliomas. N Engl J Med 2009; 360(8): 765-773
doi: 10.1056/NEJMoa0808710 pmid:19228619
11 Watanabe T, Nobusawa S, Kleihues P, Ohgaki H. IDH1 mutations are early events in the development of astrocytomas and oligodendrogliomas. Am J Pathol 2009; 174(4): 1149-1153
doi: 10.2353/ajpath.2009.080958 pmid:19246647
12 Nobusawa S, Watanabe T, Kleihues P, Ohgaki H. IDH1 mutations as molecular signature and predictive factor of secondary glioblastomas. Clin Cancer Res 2009; 15(19): 6002-6007
doi: 10.1158/1078-0432.CCR-09-0715 pmid:19755387
13 van den Bent MJ, Dubbink HJ, Marie Y, Brandes AA, Taphoorn MJ, Wesseling P, Frenay M, Tijssen CC, Lacombe D, Idbaih A, van Marion R, Kros JM, Dinjens WN, Gorlia T, Sanson M. IDH1 and IDH2 mutations are prognostic but not predictive for outcome in anaplastic oligodendroglial tumors: a report of the European Organization for Research and Treatment of Cancer Brain Tumor Group. Clin Cancer Res 2010; 16(5): 1597-1604
doi: 10.1158/1078-0432.CCR-09-2902 pmid:20160062
14 Shibahara I, Sonoda Y, Kanamori M, Saito R, Yamashita Y, Kumabe T, Watanabe M, Suzuki H, Kato S, Ishioka C, Tominaga T. IDH1/2 gene status defines the prognosis and molecular profiles in patients with grade III gliomas. Int J Clin Oncol 2012; 17(6): 551-561
pmid:21971842
15 Hartmann C, Meyer J, Balss J, Capper D, Mueller W, Christians A, Felsberg J, Wolter M, Mawrin C, Wick W, Weller M, Herold-Mende C, Unterberg A, Jeuken JW, Wesseling P, Reifenberger G, von Deimling A. Type and frequency of IDH1 and IDH2 mutations are related to astrocytic and oligodendroglial differentiation and age: a study of 1,010 diffuse gliomas. Acta Neuropathol 2009; 118(4): 469-474
doi: 10.1007/s00401-009-0561-9 pmid:19554337
16 Capper D, Sahm F, Hartmann C, Meyermann R, von Deimling A, Schittenhelm J. Application of mutant IDH1 antibody to differentiate diffuse glioma from nonneoplastic central nervous system lesions and therapy-induced changes. Am J Surg Pathol 2010; 34(8): 1199-1204
doi: 10.1097/PAS.0b013e3181e7740d pmid:20661018
17 Horbinski C, Kofler J, Kelly LM, Murdoch GH, Nikiforova MN. Diagnostic use of IDH1/2 mutation analysis in routine clinical testing of formalin-fixed, paraffin-embedded glioma tissues. J Neuropathol Exp Neurol 2009; 68(12): 1319-1325
doi: 10.1097/NEN.0b013e3181c391be pmid:19915484
18 Ichimura K, Pearson DM, Kocialkowski S, B?cklund LM, Chan R, Jones DT, Collins VP. IDH1 mutations are present in the majority of common adult gliomas but rare in primary glioblastomas. Neuro-oncol 2009; 11(4): 341-347
doi: 10.1215/15228517-2009-025 pmid:19435942
19 Zhao S, Lin Y, Xu W, Jiang W, Zha Z, Wang P, Yu W, Li Z, Gong L, Peng Y, Ding J, Lei Q, Guan KL, Xiong Y. Glioma-derived mutations in IDH1 dominantly inhibit IDH1 catalytic activity and induce HIF-1alpha. Science 2009; 324(5924): 261-265
doi: 10.1126/science.1170944 pmid:19359588
20 Dang L, White D W, Gross S, Bennett B D, Bittinger M A, Driggers E M, Fantin V R, Jang H G, Jin S, Keenan M C, Marks K M, Prins R M, Ward P S, Yen K E, Liau L M, Rabinowitz J D, Cantley L C, Thompson C B, Vander Heiden M G, Su S M. Cancer-associated IDH1 mutations produce 2-hydroxyglutarate. Nature 2009;462(7274):739-744 .
doi: 10.1038/nature08617 pmid:19935646
21 Reitman ZJ, Jin G, Karoly ED, Spasojevic I, Yang J, Kinzler KW, He Y, Bigner DD, Vogelstein B, Yan H. Profiling the effects of isocitrate dehydrogenase 1 and 2 mutations on the cellular metabolome. Proc Natl Acad Sci USA 2011; 108(8): 3270-3275
doi: 10.1073/pnas.1019393108 pmid:21289278
22 Jeuken JW, von Deimling A, Wesseling P. Molecular pathogenesis of oligodendroglial tumors. J Neurooncol 2004; 70(2): 161-181
doi: 10.1007/s11060-004-2748-1 pmid:15674476
23 Bettegowda C, Agrawal N, Jiao Y, Sausen M, Wood LD, Hruban RH, Rodriguez FJ, Cahill DP, McLendon R, Riggins G, Velculescu VE, Oba-Shinjo SM, Marie SK, Vogelstein B, Bigner D, Yan H, Papadopoulos N, Kinzler KW. Mutations in CIC and FUBP1 contribute to human oligodendroglioma. Science 2011; 333(6048): 1453-1455
doi: 10.1126/science.1210557 pmid:21817013
24 Scheie D, Cvancarova M, M?rk S, Skullerud K, Andresen PA, Benestad I, Helseth E, Meling T, Beiske K. Can morphology predict 1p/19q loss in oligodendroglial tumours? Histopathology 2008; 53(5): 578-587
doi: 10.1111/j.1365-2559.2008.03160.x pmid:18983467
25 Wick W, Hartmann C, Engel C, Stoffels M, Felsberg J, Stockhammer F, Sabel MC, Koeppen S, Ketter R, Meyermann R, Rapp M, Meisner C, Kortmann RD, Pietsch T, Wiestler OD, Ernemann U, Bamberg M, Reifenberger G, von Deimling A, Weller M. NOA-04 randomized phase III trial of sequential radiochemotherapy of anaplastic glioma with procarbazine, lomustine, and vincristine or temozolomide. J Clin Oncol 2009; 27(35): 5874-5880
doi: 10.1200/JCO.2009.23.6497 pmid:19901110
26 Cairncross G, Berkey B, Shaw E, Jenkins R, Scheithauer B, Brachman D, Buckner J, Fink K, Souhami L, Laperierre N, Mehta M, Curran W. Phase III trial of chemotherapy plus radiotherapy compared with radiotherapy alone for pure and mixed anaplastic oligodendroglioma: Intergroup Radiation Therapy Oncology Group Trial 9402. J Clin Oncol 2006; 24(18): 2707-2714
doi: 10.1200/JCO.2005.04.3414 pmid:16782910
27 van den Bent MJ, Carpentier AF, Brandes AA, Sanson M, Taphoorn MJ, Bernsen HJ, Frenay M, Tijssen CC, Grisold W, Sipos L, Haaxma-Reiche H, Kros JM, van Kouwenhoven MC, Vecht CJ, Allgeier A, Lacombe D, Gorlia T. Adjuvant procarbazine, lomustine, and vincristine improves progression-free survival but not overall survival in newly diagnosed anaplastic oligodendrogliomas and oligoastrocytomas: a randomized European Organisation for Research and Treatment of Cancer phase III trial. J Clin Oncol 2006; 24(18): 2715-2722
doi: 10.1200/JCO.2005.04.6078 pmid:16782911
28 Kouwenhoven MCM, Kros JM, French PJ, Biemond-ter Stege EM, Graveland WJ, Taphoorn MJB, Brandes AA, van den Bent MJ. 1p/19q loss within oligodendroglioma is predictive for response to first line temozolomide but not to salvage treatment. Eur J Cancer 2006; 42(15): 2499-2503
doi: 10.1016/j.ejca.2006.05.021 pmid:16914310
29 Cancer Genome Atlas Research Network. Comprehensive genomic characterization defines human glioblastoma genes and core pathways. Nature 2008; 455(7216): 1061-1068
doi: 10.1038/nature07385 pmid:18772890
30 Wong AJ, Ruppert JM, Bigner SH, Grzeschik CH, Humphrey PA, Bigner DS, Vogelstein B. Structural alterations of the epidermal growth factor receptor gene in human gliomas. Proc Natl Acad Sci USA 1992; 89(7): 2965-2969
doi: 10.1073/pnas.89.7.2965 pmid:1557402
31 Hurtt MR, Moossy J, Donovan-Peluso M, Locker J. Amplification of epidermal growth factor receptor gene in gliomas: histopathology and prognosis. J Neuropathol Exp Neurol 1992; 51(1): 84-90
doi: 10.1097/00005072-199201000-00010 pmid:1311022
32 Lino MM, Merlo A. PI3Kinase signaling in glioblastoma. J Neurooncol 2011; 103(3): 417-427
doi: 10.1007/s11060-010-0442-z pmid:21063898
33 Gan HK, Kaye AH, Luwor RB. The EGFRvIII variant in glioblastoma multiforme. J Clin Neurosci 2009; 16(6): 748-754
doi: 10.1016/j.jocn.2008.12.005 pmid:19324552
34 Hatanpaa KJ, Burma S, Zhao D, Habib AA. Epidermal growth factor receptor in glioma: signal transduction, neuropathology, imaging, and radioresistance. Neoplasia 2010; 12(9): 675-684
pmid:20824044
35 Aldape KD, Ballman K, Furth A, Buckner JC, Giannini C, Burger PC, Scheithauer BW, Jenkins RB, James CD. Immunohistochemical detection of EGFRvIII in high malignancy grade astrocytomas and evaluation of prognostic significance. J Neuropathol Exp Neurol 2004; 63(7): 700-707
pmid:15290895
36 Knobbe CB, Merlo A, Reifenberger G. Pten signaling in gliomas. Neuro Oncol 2002; 4(3): 196-211
pmid:12084351
37 Ohgaki H, Kleihues P. Genetic alterations and signaling pathways in the evolution of gliomas. Cancer Sci 2009; 100(12): 2235-2241
doi: 10.1111/j.1349-7006.2009.01308.x pmid:19737147
38 Koul D. PTEN signaling pathways in glioblastoma. Cancer Biol Ther 2008; 7(9): 1321-1325
doi: 10.4161/cbt.7.9.6954 pmid:18836294
39 Busch C, Geisler J, Knappskog S, Lillehaug JR, L?nning PE. Alterations in the p53 pathway and p16INK4a expression predict overall survival in metastatic melanoma patients treated with dacarbazine. J Invest Dermatol 2010; 130(10): 2514-2516
doi: 10.1038/jid.2010.138 pmid:20505745
40 Silber JR, Bobola MS, Blank A, Chamberlain MC. O(6)-methylguanine-DNA methyltransferase in glioma therapy: promise and problems. Biochim Biophys Acta 2012; 1826(1): 71-82
pmid:22244911
41 Hegi ME, Diserens AC, Gorlia T, Hamou MF, de Tribolet N, Weller M, Kros JM, Hainfellner JA, Mason W, Mariani L, Bromberg JE, Hau P, Mirimanoff RO, Cairncross JG, Janzer RC, Stupp R. MGMT gene silencing and benefit from temozolomide in glioblastoma. N Engl J Med 2005; 352(10): 997-1003
doi: 10.1056/NEJMoa043331 pmid:15758010
42 Olson RA, Brastianos PK, Palma DA. Prognostic and predictive value of epigenetic silencing of MGMT in patients with high grade gliomas: a systematic review and meta-analysis. J Neurooncol 2011; 105(2): 325-335
doi: 10.1007/s11060-011-0594-5 pmid:21523485
43 Gorlia T, van den Bent MJ, Hegi ME, Mirimanoff RO, Weller M, Cairncross JG, Eisenhauer E, Belanger K, Brandes AA, Allgeier A, Lacombe D, Stupp R. Nomograms for predicting survival of patients with newly diagnosed glioblastoma: prognostic factor analysis of EORTC and NCIC trial 26981-22981/CE.3. Lancet Oncol 2008; 9(1): 29-38
doi: 10.1016/S1470-2045(07)70384-4 pmid:18082451
44 Rivera AL, Pelloski CE, Gilbert MR, Colman H, De La Cruz C, Sulman EP, Bekele BN, Aldape KD. MGMT promoter methylation is predictive of response to radiotherapy and prognostic in the absence of adjuvant alkylating chemotherapy for glioblastoma. Neuro-oncol 2010; 12(2): 116-121
doi: 10.1093/neuonc/nop020 pmid:20150378
45 Minniti G, Salvati M, Arcella A, Buttarelli F, D’Elia A, Lanzetta G, Esposito V, Scarpino S, Maurizi Enrici R, Giangaspero F. Correlation between O6-methylguanine-DNA methyltransferase and survival in elderly patients with glioblastoma treated with radiotherapy plus concomitant and adjuvant temozolomide. J Neurooncol 2011; 102(2): 311-316
doi: 10.1007/s11060-010-0324-4 pmid:20686820
46 Combs SE, Rieken S, Wick W, Abdollahi A, von Deimling A, Debus J, Hartmann C. Prognostic significance of IDH-1 and MGMT in patients with glioblastoma: one step forward, and one step back? Radiat Oncol 2011; 6(1): 115
doi: 10.1186/1748-717X-6-115 pmid:21910919
47 Brandes AA, Franceschi E, Tosoni A, Bartolini S, Bacci A, Agati R, Ghimenton C, Turazzi S, Talacchi A, Skrap M, Marucci G, Volpin L, Morandi L, Pizzolitto S, Gardiman M, Andreoli A, Calbucci F, Ermani M. O(6)-methylguanine DNA-methyltransferase methylation status can change between first surgery for newly diagnosed glioblastoma and second surgery for recurrence: clinical implications. Neuro-oncol 2010; 12(3): 283-288
doi: 10.1093/neuonc/nop050 pmid:20167816
48 Hegi ME, Diserens AC, Godard S, Dietrich PY, Regli L, Ostermann S, Otten P, Van Melle G, de Tribolet N, Stupp R. Clinical trial substantiates the predictive value of O-6-methylguanine-DNA methyltransferase promoter methylation in glioblastoma patients treated with temozolomide. Clin Cancer Res 2004; 10(6): 1871-1874
doi: 10.1158/1078-0432.CCR-03-0384 pmid:15041700
49 van den Bent MJ, Dubbink HJ, Sanson M, van der Lee-Haarloo CR, Hegi M, Jeuken JW, Ibdaih A, Brandes AA, Taphoorn MJ, Frenay M, Lacombe D, Gorlia T, Dinjens WN, Kros JM. MGMT promoter methylation is prognostic but not predictive for outcome to adjuvant PCV chemotherapy in anaplastic oligodendroglial tumors: a report from EORTC Brain Tumor Group Study 26951. J Clin Oncol 2009; 27(35): 5881-5886
doi: 10.1200/JCO.2009.24.1034 pmid:19901104
50 Phillips HS, Kharbanda S, Chen R, Forrest WF, Soriano RH, Wu TD, Misra A, Nigro JM, Colman H, Soroceanu L, Williams PM, Modrusan Z, Feuerstein BG, Aldape K. Molecular subclasses of high-grade glioma predict prognosis, delineate a pattern of disease progression, and resemble stages in neurogenesis. Cancer Cell 2006; 9(3): 157-173
doi: 10.1016/j.ccr.2006.02.019 pmid:16530701
51 Verhaak RG, Hoadley KA, Purdom E, Wang V, Qi Y, Wilkerson MD, Miller CR, Ding L, Golub T, Mesirov JP, Alexe G, Lawrence M, O’Kelly M, Tamayo P, Weir BA, Gabriel S, Winckler W, Gupta S, Jakkula L, Feiler HS, Hodgson JG, James CD, Sarkaria JN, Brennan C, Kahn A, Spellman PT, Wilson RK, Speed TP, Gray JW, Meyerson M, Getz G, Perou CM, Hayes DN. Integrated genomic analysis identifies clinically relevant subtypes of glioblastoma characterized by abnormalities in PDGFRA, IDH1, EGFR, and NF1. Cancer Cell 2010; 17(1): 98-110
doi: 10.1016/j.ccr.2009.12.020 pmid:20129251
52 Toyota M, Ahuja N, Ohe-Toyota M, Herman JG, Baylin SB, Issa JP. CpG island methylator phenotype in colorectal cancer. Proc Natl Acad Sci USA 1999; 96(15): 8681-8686
doi: 10.1073/pnas.96.15.8681 pmid:10411935
53 Noushmehr H, Weisenberger DJ, Diefes K, Phillips HS, Pujara K, Berman BP, Pan F, Pelloski CE, Sulman EP, Bhat KP, Verhaak RG, Hoadley KA, Hayes DN, Perou CM, Schmidt HK, Ding L, Wilson RK, Van Den Berg D, Shen H, Bengtsson H, Neuvial P, Cope LM, Buckley J, Herman JG, Baylin SB, Laird PW, Aldape K. Identification of a CpG island methylator phenotype that defines a distinct subgroup of glioma. Cancer Cell 2010; 17(5): 510-522
doi: 10.1016/j.ccr.2010.03.017 pmid:20399149
[1] Li Shang, Mingrong Wang. Molecular alterations and clinical relevance in esophageal squamous cell carcinoma[J]. Front Med, 2013, 7(4): 401-410.
[2] Qiang Gao, Yinghong Shi, Xiaoying Wang, Jian Zhou, Shuangjian Qiu, Jia Fan. Translational medicine in hepatocellular carcinoma[J]. Front Med, 2012, 6(2): 122-133.
Viewed
Full text


Abstract

Cited

  Shared   
  Discussed