Abstract
Mutations at the codon 132 in the isocitrate dehydrogenase 1 (IDH1) gene occur early, with a high frequency, in World Health Organization (WHO) grade II gliomas. We investigated the impact of IDH1 mutations on spontaneous glioma growth rate, known to be an early prognostic factor.The mean tumor diameter was assessed on the first MRI performed at diagnosis and on a second MRI, performed immediately before surgery, in a series of 64 WHO grade II gliomas. The patients did not undergo treatment before surgery. Because of a frequent association, we jointly analyzed the 1p19q co-deletion and IDH1 mutations effects on tumor velocity of diameter expansion (mm/year) during preoperative spontaneous growth period. 1p19q co-deletion had a significant slowing effect (p = 0.0133) on tumor growth estimated at −1.7760 ± 0.711 mm/year (95% CI −3.154, −0.366), whereas IDH1 mutations estimated effect of +0.036 ± 0.833 mm/year (95% CI −1.668; +1.596) was not significant (p = 0.9654). Our results provide first evidence that IDH1 mutations are not significantly involved in tumor growth rate. By contrast, we confirm that 1p19q co-deletion decreases growth velocity.
Similar content being viewed by others
References
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, Hartigan J, Smith DR, Strausberg RL, Nagahashi Marie SK, Oba Shinjo SM, Yan H, Riggins GJ, Bigner DD, Karchin R, Papadopoulos N, Parmigiani G, Vogelstein B, Velculescu VE, Kinzler KW (2008) An integrated genomic analysis of human glioblastoma multiforme. Science 321:1807–1812
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 (2009) IDH1 and IDH2 mutations in gliomas. N Engl J Med 360:765–773
Watanabe T, Nobusawa S, Kleihues P, Ohgaki H (2009) IDH1 mutations are early events in the development of astrocytomas and oligodendrogliomas. Am J Pathol 174:1149–1153
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 (2009) 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 118:469–474
Sanson M, Marie Y, Paris S, Idbaih A, Laffaire J, Ducray F, El Hallani S, Boisselier B, Mokhtari K, Hoang-Xuan K, Delattre JY (2009) Isocitrate dehydrogenase 1 codon 132 mutation is an important prognostic biomarker in gliomas. J Clin Oncol 27:4150–4154
Kim YH, Nobusawa S, Mittelbronn M, Paulus W, Brokinkel B, Keyvani K, Sure U, Wrede K, Nakazato Y, Tanaka Y, Vital A, Mariani L, Stawski R, Watanabe T, De Girolami U, Kleihues P, Ohgaki H (2009) Molecular classification of low-grade diffuse gliomas. Am J Pathol 177:2708–2714
Houillier C, Wang X, Kaloshi G, Mokhtari K, Guillevin R, Laffaire J, Paris S, Boisselier B, Idbaih A, Laigle-Donadey F, Hoang-Xuan K, Sanson M, Delattre JY (2010) IDH1 or IDH2 mutations predict longer survival and response to temozolomide in low-grade gliomas. Neurology 75:1560–1566
Metellus P, Coulibaly B, Colin C, de Paula AM, Vasiljevic A, Taieb D, Barlier A, Boisselier B, Mokhtari K, Wang XW, Loundou A, Chapon F, Pineau S, Ouafik L, Chinot O, Figarella-Branger D (2010) Absence of IDH mutation identifies a novel radiologic and molecular subtype of WHO grade II gliomas with dismal prognosis. Acta Neuropathol 120:719–729
Mandonnet E, Delattre JY, Tanguy ML, Swanson KR, Carpentier AF, Duffau H, Cornu P, Van Effenterre R, Alvord EC Jr, Capelle L (2003) Continuous growth of mean tumor diameter in a subset of grade II gliomas. Ann Neurol 53:524–528
Pallud J, Mandonnet E, Duffau H, Kujas M, Guillevin R, Galanaud D, Taillandier L, Capelle L (2006) Prognostic value of initial magnetic resonance imaging growth rates for World Health Organization grade II gliomas. Ann Neurol 60:380–383
Cairncross JG, Ueki K, Zlatescu MC, Lisle DK, Finkelstein DM, Hammond RR, Silver JS, Stark PC, Macdonald DR, Ino Y, Ramsay DA, Louis DN (1998) Specific genetic predictors of chemotherapeutic response and survival in patients with anaplastic oligodendrogliomas. J Natl Cancer Inst 90:1473–1479
Dehais C, Laigle-Donadey F, Marie Y, Kujas M, Lejeune J, Benouaich-Amiel A, Pedretti M, Polivka M, Xuan KH, Thillet J, Delattre JY, Sanson M (2006) Prognostic stratification of patients with anaplastic gliomas according to genetic profile. Cancer 107:1891–1897
Jenkins RB, Blair H, Ballman KV, Giannini C, Arusell RM, Law M, Flynn H, Passe S, Felten S, Brown PD, Shaw EG, Buckner JC (2006) A t(1;19)(q10;p10) mediates the combined deletions of 1p and 19q and predicts a better prognosis of patients with oligodendroglioma. Cancer Res 66:9852–9861
Kujas M, Lejeune J, Benouaich-Amiel A, Criniere E, Laigle-Donadey F, Marie Y, Mokhtari K, Polivka M, Bernier M, Chretien F, Couvelard A, Capelle L, Duffau H, Cornu P, Broët P, Thillet J, Carpentier AF, Sanson M, Hoang-Xuan K, Delattre JY (2005) Chromosome 1p loss: a favorable prognostic factor in low-grade gliomas. Ann Neurol 58:322–326
Iwamoto FM, Nicolardi L, Demopoulos A, Barbashina V, Salazar P, Rosenblum M, Hormigo A (2008) Clinical relevance of 1p and 19q deletion for patients with WHO grade 2 and 3 gliomas. J Neurooncol 88:293–298
Mariani L, Deiana G, Vassella E, Fathi AR, Murtin C, Arnold M, Vajtai I, Weis J, Siegenthaler P, Schobesberger M, Reinert MM (2006) Loss of heterozygosity 1p36 and 19q13 is a prognostic factor for overall survival in patients with diffuse WHO grade 2 gliomas treated without chemotherapy. J Clin Oncol 24:4758–4763
van den Bent MJ, Looijenga LH, Langenberg K, Dinjens W, Graveland W, Uytdewilligen L, Sillevis Smitt PA, Jenkins RB, Kros JM (2003) Chromosomal anomalies in oligodendroglial tumors are correlated with clinical features. Cancer 97:1276–1284
Ricard D, Kaloshi G, Amiel-Benouaich A, Lejeune J, Marie Y, Mandonnet E, Kujas M, Mokhtari K, Taillibert S, Laigle-Donadey F, Carpentier AF, Omuro A, Capelle L, Duffau H, Cornu P, Guillevin R, Sanson M, Hoang-Xuan K, Delattre JY (2007) Dynamic history of low-grade gliomas before and after temozolomide treatment. Ann Neurol 61:484–490
Labussiere M, Idbaih A, Wang XW, Marie Y, Boisselier B, Falet C, Paris S, Laffaire J, Carpentier C, Criniere E, Ducray F, El Hallani S, Mokhtari K, Hoang-Xuan K, Delattre JY, Sanson M (2010) All the 1p19q codeleted gliomas are mutated on IDH1 or IDH2. Neurology 74:1886–1890
Miller SA, Dykes DD, Polesky HF (1988) A simple salting out procedure for extracting DNA from human nucleated cells. Nucleic Acids Res 16:1215
Balss J, Meyer J, Mueller W, Korshunov A, Hartmann C, von Deimling A (2008) Analysis of the IDH1 codon 132 mutation in brain tumors. Acta Neuropathol 116:597–602
Vet JA, Bringuier PP, Schaafsma HE, Witjes JA, Debruyne FM, Schalken JA (1995) Comparison of P53 protein overexpression with P53 mutation in bladder cancer: clinical and biologic aspects. Lab Invest 73:837–843
Anker L, Ohgaki H, Ludeke BI, Herrmann HD, Kleihues P, Westphal M (1993) p53 Protein accumulation and gene mutations in human glioma cell lines. Int J Cancer 55:982–987
Louis DN, von Deimling A, Chung RY, Rubio MP, Whaley JM, Eibl RH, Ohgaki H, Wiestler OD, Thor AD, Seizinger BR (1993) Comparative study of p53 gene and protein alterations in human astrocytic tumors. J Neuropathol Exp Neurol 52:31–38
Peraud A, Kreth FW, Wiestler OD, Kleihues P, Reulen HJ (2002) Prognostic impact of TP53 mutations and P53 protein overexpression in supratentorial WHO grade II astrocytomas and oligoastrocytomas. Clin Cancer Res 8:1117–1124
Fisher RA (1925) Statistical methods for research workers. Oliver and Boyd, Edinburgh
Yates F (1933) The principles of orthogonality and confounding in replicated experiments. J Agric Sci 23:108–145
Yates F (1934) The analysis of multiple classifications with unequal numbers in the different classes. J Am Stat Soc 29:51–66
Huber PJ (1973) Robust regression: asymptotis, conjecture and Monte Carlo. Ann Stat 1:799–821
Mandonnet E, Pallud J, Fontaine D, Taillandier L, Bauchet L, Peruzzi P, Guyotat J, Bernier V, Baron MH, Duffau H, Capelle L (2010) Inter- and intrapatients comparison of WHO grade II glioma kinetics before and after surgical resection. Neurosurg Rev 33:91–96
Smith JS, Chang EF, Lamborn KR, Chang SM, Prados MD, Cha S, Tihan T, Vandenberg S, McDermott MW, Berger MS (2008) Role of extent of resection in the long-term outcome of low-grade hemispheric gliomas. J Clin Oncol 26:1338–1345
Dang L, White DW, Gross S, Bennett BD, Bittinger MA, Driggers EM, Fantin VR, Jang HG, Jin S, Keenan MC, Marks KM, Prins RM, Ward PS, Yen KE, Liau LM, Rabinowitz LC, Thompson CB, Vander Heiden MG, Su SM (2009) Cancer-associated IDH1 mutations produce 2-hydroxyglutarate. Nature 462:739–744
Xu W, Yang H, Liu Y, Yang Y, Wang P, Kim SH, Ito S, Yang C, Wang P, Xiao MT, Liu LX, Jiang WQ, Liu J, Zhang JY, Wang B, Frye S, Zhang Y, Xu YH, Lei QY, Guan KL, Zhao SM, Xiong Y (2011) Oncometabolite 2-hydroxyglutarate is a competitive inhibitor of alpha-ketoglutarate-dependent dioxygenases. Cancer Cell 19:17–30
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, Cancer Genome Atlas Research Network (2010) Identification of a CpG island methylator phenotype that defines a distinct subgroup of glioma. Cancer Cell 17:510–522
Pusch S, Sahm F, Meyer J, Mittelbronn M, Hartmann C, Von Deimling A (2011) Glioma IDH1 mutation patterns off the beaten track. Neuropathol Appl Neurobiol 37:428–430
Dubbink HJ, Taal W, van Marion R, Kros JM, van Heuvel I, Bromberg JE, Zonnenberg BA, Zonnenberg CB, Postma TJ, Gijtenbeek JM, Boogerd W, Groenendijk FH, Sillevis Smith PA, Dinjens WN, van den Bent MJ (2009) IDH1 mutations in low-grade astrocytomas predict survival but not response to temozolomide. Neurology 73:1792–1795
Acknowledgment
This work was supported by a grant of the Ligue Nationale contre le Cancer, Comité du Gard, France.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Gozé, C., Bezzina, C., Gozé, E. et al. 1P19Q loss but not IDH1 mutations influences WHO grade II gliomas spontaneous growth. J Neurooncol 108, 69–75 (2012). https://doi.org/10.1007/s11060-012-0831-6
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11060-012-0831-6