nach oben

Erschienen in:

11.09.2017 | Diagnostic Neuroradiology

New prognostic factor telomerase reverse transcriptase promotor mutation presents without MR imaging biomarkers in primary glioblastoma

verfasst von: Tunc F. Ersoy, Vera C. Keil, Dariusch R. Hadizadeh, Gerrit H. Gielen, Rolf Fimmers, Andreas Waha, Barbara Heidenreich, Rajiv Kumar, Hans H. Schild, Matthias Simon

Erschienen in: Neuroradiology | Ausgabe 12/2017

Einloggen, um Zugang zu erhalten

Abstract

Purpose

Magnetic resonance (MR) imaging biomarkers can assist in the non-invasive assessment of the genetic status in glioblastomas (GBMs). Telomerase reverse transcriptase (TERT) promoter mutations are associated with a negative prognosis. This study was performed to identify MR imaging biomarkers to forecast the TERT mutation status.

Methods

Pre-operative MRIs of 64/67 genetically confirmed primary GBM patients (51/67 TERT-mutated with rs2853669 polymorphism) were analyzed according to Visually AcceSAble Rembrandt Images (VASARI) (https://wiki.cancerimagingarchive.net/display/Public/VASARI+Research+Project) imaging criteria by three radiological raters. TERT mutation and O⁶-methylguanine-DNA methyltransferase (MGMT) hypermethylation data were obtained through direct and pyrosequencing as described in a previous study. Clinical data were derived from a prospectively maintained electronic database. Associations of potential imaging biomarkers and genetic status were assessed by Fisher and Mann-Whitney U tests and stepwise linear regression.

Results

No imaging biomarkers could be identified to predict TERT mutational status (alone or in conjunction with TERT promoter polymorphism rs2853669 AA-allele). TERT promoter mutations were more common in patients with tumor-associated seizures as first symptom (26/30 vs. 25/37, p = 0.07); these showed significantly smaller tumors [13.1 (9.0–19.0) vs. 24.0 (16.6–37.5) all cm³; p = 0.007] and prolonged median overall survival [17.0 (11.5–28.0) vs. 9.0 (4.0–12.0) all months; p = 0.02]. TERT-mutated GBMs were underrepresented in the extended angularis region (p = 0.03), whereas MGMT-methylated GBMs were overrepresented in the corpus callosum (p = 0.03) and underrepresented temporomesially (p = 0.01).

Conclusion

Imaging biomarkers for prediction of TERT mutation status remain weak and cannot be derived from the VASARI protocol. Tumor-associated seizures are less common in TERT mutated glioblastomas.

Nur mit Berechtigung zugänglich

Stupp R, Hegi ME, Mason WP, van den Bent MJ, Taphoorn MJ, Janzer RC et al (2009) Effects of radiotherapy with concomitant and adjuvant temozolomide versus radiotherapy alone on survival in glioblastoma in a randomised phase III study: 5-year analysis of the EORTC-NCIC trial. Lancet Oncol 10(5):459–466. https://doi.org/10.1016/S1470-2045(09)70025-7 CrossRefPubMed

Koshy M, Villano JL, Dolecek TA, Howard A, Mahmood U, Chmura SJ et al (2012) Improved survival time trends for glioblastoma using the SEER 17 population-based registries. J Neuro-Oncol 107(1):207–212. https://doi.org/10.1007/s11060-011-0738-7 CrossRef

Gilbert MR, Sulman EP, Mehta MP (2014) Bevacizumab for newly diagnosed glioblastoma. N Engl J Med 370(21):2048–2049. https://doi.org/10.1056/NEJMc1403303 CrossRefPubMed

Ostrom QT, Gittleman H, Fulop J, Liu M, Blanda R, Kromer C et al (2015) CBTRUS statistical report: primary brain and central nervous system tumors diagnosed in the United States in 2008-2012. Neuro Oncol 17(Suppl 4):iv1–iv62. https://doi.org/10.1093/neuonc/nov189 CrossRefPubMedPubMedCentral

Louis DN, Perry A, Reifenberger G, von Deimling A, Figarella-Branger D, Cavenee WK et al (2016) The 2016 World Health Organization classification of tumors of the central nervous system: a summary. Acta Neuropathol 131(6):803–820. https://doi.org/10.1007/s00401-016-1545-1 CrossRefPubMed

Lote K, Stenwig AE, Skullerud K, Hirschberg H (1998) Prevalence and prognostic significance of epilepsy in patients with gliomas. Eur J Cancer 34(1):98–102CrossRefPubMed

Lacroix M, Abi-Said D, Fourney DR, Gokaslan ZL, Shi W, DeMonte F et al (2001) A multivariate analysis of 416 patients with glioblastoma multiforme: prognosis, extent of resection, and survival. J Neurosurg 95(2):190–198. https://doi.org/10.3171/jns.2001.95.2.0190 CrossRefPubMed

Ohgaki H, Dessen P, Jourde B, Horstmann S, Nishikawa T, Di Patre PL et al (2004) Genetic pathways to glioblastoma: a population-based study. Cancer Res 64(19):6892–6899. https://doi.org/10.1158/0008-5472.CAN-04-1337 CrossRefPubMed

Bleeker FE, Molenaar RJ, Leenstra S (2012) Recent advances in the molecular understanding of glioblastoma. J Neuro-Oncol 108(1):11–27. https://doi.org/10.1007/s11060-011-0793-0 CrossRef

10.

Sottoriva A, Spiteri I, Piccirillo SG, Touloumis A, Collins VP, Marioni JC et al (2013) Intratumor heterogeneity in human glioblastoma reflects cancer evolutionary dynamics. Proc Natl Acad Sci U S A 110(10):4009–4014. https://doi.org/10.1073/pnas.1219747110 CrossRefPubMedPubMedCentral

11.

Ellis HP, Greenslade M, Powell B, Spiteri I, Sottoriva A, Kurian KM (2015) Current challenges in glioblastoma: intratumour heterogeneity, residual disease, and models to predict disease recurrence. Front Oncol 5:251. https://doi.org/10.3389/fonc.2015.00251 CrossRefPubMedPubMedCentral

12.

YT O, Cho HJ, Kim J, Lee JH, Rho K, Seo YJ et al (2014) Translational validation of personalized treatment strategy based on genetic characteristics of glioblastoma. PLoS One 9(8):e103327. https://doi.org/10.1371/journal.pone.0103327 CrossRef

13.

Riemenschneider MJ, Jeuken JW, Wesseling P, Reifenberger G (2010) Molecular diagnostics of gliomas: state of the art. Acta Neuropathol 120(5):567–584. https://doi.org/10.1007/s00401-010-0736-4 CrossRefPubMedPubMedCentral

14.

Killela PJ, Reitman ZJ, Jiao Y, Bettegowda C, Agrawal N, Diaz LA Jr et al (2013) TERT promoter mutations occur frequently in gliomas and a subset of tumors derived from cells with low rates of self-renewal. Proc Natl Acad Sci U S A 110(15):6021–6026. https://doi.org/10.1073/pnas.1303607110 CrossRefPubMedPubMedCentral

15.

Simon M, Hosen I, Gousias K, Rachakonda S, Heidenreich B, Gessi M et al (2015) TERT promoter mutations: a novel independent prognostic factor in primary glioblastomas. Neuro-Oncology 17(1):45–52. https://doi.org/10.1093/neuonc/nou158 CrossRefPubMed

16.

Mosrati MA, Malmstrom A, Lysiak M, Krysztofiak A, Hallbeck M, Milos P et al (2015) TERT promoter mutations and polymorphisms as prognostic factors in primary glioblastoma. Oncotarget 6(18):16663–16673. 10.18632/oncotarget.4389 CrossRefPubMedPubMedCentral

17.

Spiegl-Kreinecker S, Lotsch D, Ghanim B, Pirker C, Mohr T, Laaber M et al (2015) Prognostic quality of activating TERT promoter mutations in glioblastoma: interaction with the rs2853669 polymorphism and patient age at diagnosis. Neuro-Oncology 17(9):1231–1240. https://doi.org/10.1093/neuonc/nov010 CrossRefPubMedPubMedCentral

18.

Nencha U, Rahimian A, Giry M, Sechi A, Mokhtari K, Polivka M et al (2016) TERT promoter mutations and rs2853669 polymorphism: prognostic impact and interactions with common alterations in glioblastomas. J Neuro-Oncol 126(3):441–446. https://doi.org/10.1007/s11060-015-1999-3 CrossRef

19.

Aghi M, Gaviani P, Henson JW, Batchelor TT, Louis DN, Barker FG 2nd (2005) Magnetic resonance imaging characteristics predict epidermal growth factor receptor amplification status in glioblastoma. Clin Cancer Res: Off J Am Assoc Cancer Res 11(24 Pt 1):8600–8605. https://doi.org/10.1158/1078-0432.CCR-05-0713 CrossRef

20.

Zinn PO, Sathyan P, Mahajan B, Bruyere J, Hegi M, Majumder S et al (2012) A novel volume-age-KPS (VAK) glioblastoma classification identifies a prognostic cognate microRNA-gene signature. PLoS One 7(8):e41522. https://doi.org/10.1371/journal.pone.0041522 CrossRefPubMedPubMedCentral

21.

Jain R, Poisson L, Narang J, Gutman D, Scarpace L, Hwang SN et al (2013) Genomic mapping and survival prediction in glioblastoma: molecular subclassification strengthened by hemodynamic imaging biomarkers. Radiology 267(1):212–220. https://doi.org/10.1148/radiol.12120846 CrossRefPubMedPubMedCentral

22.

Colen RR, Vangel M, Wang J, Gutman DA, Hwang SN, Wintermark M et al (2014) Imaging genomic mapping of an invasive MRI phenotype predicts patient outcome and metabolic dysfunction: a TCGA glioma phenotype research group project. BMC Med Genet 7:30. https://doi.org/10.1186/1755-8794-7-30

23.

Pope WB, Chen JH, Dong J, Carlson MR, Perlina A, Cloughesy TF et al (2008) Relationship between gene expression and enhancement in glioblastoma multiforme: exploratory DNA microarray analysis. Radiology 249(1):268–277. https://doi.org/10.1148/radiol.2491072000 CrossRefPubMedPubMedCentral

24.

Diehn M, Nardini C, Wang DS, McGovern S, Jayaraman M, Liang Y et al (2008) Identification of noninvasive imaging surrogates for brain tumor gene-expression modules. Proc Natl Acad Sci U S A 105(13):5213–5218. https://doi.org/10.1073/pnas.0801279105 CrossRefPubMedPubMedCentral

25.

Rao A, Rao G, Gutman DA, Flanders AE, Hwang SN, Rubin DL et al (2015) A combinatorial radiographic phenotype may stratify patient survival and be associated with invasion and proliferation characteristics in glioblastoma. J Neurosurg:1–10. https://doi.org/10.3171/2015.4.JNS142732

26.

Buckner JC (2003) Factors influencing survival in high-grade gliomas. Semin Oncol 30(6 Suppl 19):10–14CrossRefPubMed

27.

Lamborn KR, Chang SM, Prados MD (2004) Prognostic factors for survival of patients with glioblastoma: recursive partitioning analysis. Neuro-Oncology 6(3):227–235. https://doi.org/10.1215/S1152851703000620 CrossRefPubMedPubMedCentral

28.

Li SW, Qiu XG, Chen BS, Zhang W, Ren H, Wang ZC et al (2009) Prognostic factors influencing clinical outcomes of glioblastoma multiforme. Chin Med J 122(11):1245–1249PubMed

29.

Colen RR, Wang J, Singh SK, Gutman DA, Zinn PO (2015) Glioblastoma: imaging genomic mapping reveals sex-specific oncogenic associations of cell death. Radiology 275(1):215–227. https://doi.org/10.1148/radiol.14141800 CrossRefPubMed

30.

Armstrong TS, Grant R, Gilbert MR, Lee JW, Norden AD (2016) Epilepsy in glioma patients: mechanisms, management, and impact of anticonvulsant therapy. Neuro-Oncology 18(6):779–789. https://doi.org/10.1093/neuonc/nov269 CrossRefPubMed

31.

Drabycz S, Roldan G, de Robles P, Adler D, McIntyre JB, Magliocco AM et al (2010) An analysis of image texture, tumor location, and MGMT promoter methylation in glioblastoma using magnetic resonance imaging. NeuroImage 49(2):1398–1405. https://doi.org/10.1016/j.neuroimage.2009.09.049 CrossRefPubMed

32.

Carrillo JA, Lai A, Nghiemphu PL, Kim HJ, Phillips HS, Kharbanda S et al (2012) Relationship between tumor enhancement, edema, IDH1 mutational status, MGMT promoter methylation, and survival in glioblastoma. AJNR Am J Neuroradiol 33(7):1349–1355. https://doi.org/10.3174/ajnr.A2950 CrossRefPubMed

33.

Ellingson BM, Cloughesy TF, Pope WB, Zaw TM, Phillips H, Lalezari S et al (2012) Anatomic localization of O6-methylguanine DNA methyltransferase (MGMT) promoter methylated and unmethylated tumors: a radiographic study in 358 de novo human glioblastomas. NeuroImage 59(2):908–916. https://doi.org/10.1016/j.neuroimage.2011.09.076 CrossRefPubMed

34.

Moon WJ, Choi JW, Roh HG, Lim SD, Koh YC (2012) Imaging parameters of high grade gliomas in relation to the MGMT promoter methylation status: the CT, diffusion tensor imaging, and perfusion MR imaging. Neuroradiology 54(6):555–563. https://doi.org/10.1007/s00234-011-0947-y CrossRefPubMed

35.

Ahn SS, Shin NY, Chang JH, Kim SH, Kim EH, Kim DW et al (2014) Prediction of methylguanine methyltransferase promoter methylation in glioblastoma using dynamic contrast-enhanced magnetic resonance and diffusion tensor imaging. J Neurosurg 121(2):367–373. https://doi.org/10.3171/2014.5.JNS132279 CrossRefPubMed

36.

Mikeska T, Bock C, El-Maarri O, Hubner A, Ehrentraut D, Schramm J et al (2007) Optimization of quantitative MGMT promoter methylation analysis using pyrosequencing and combined bisulfite restriction analysis. J Mol Diagn 9(3):368–381. https://doi.org/10.2353/jmoldx.2007.060167 CrossRefPubMedPubMedCentral

37.

Rothman KJ (1990) No adjustments are needed for multiple comparisons. Epidemiology 1(1):43–46CrossRefPubMed

38.

Perreault S, Ramaswamy V, Achrol AS, Chao K, Liu TT, Shih D et al (2014) MRI surrogates for molecular subgroups of medulloblastoma. AJNR Am J Neuroradiol 35(7):1263–1269. https://doi.org/10.3174/ajnr.A3990 CrossRefPubMedPubMedCentral

39.

Iliadis G, Kotoula V, Chatzisotiriou A, Televantou D, Eleftheraki AG, Lambaki S et al (2012) Volumetric and MGMT parameters in glioblastoma patients: survival analysis. BMC Cancer 12:3. https://doi.org/10.1186/1471-2407-12-3 CrossRefPubMedPubMedCentral

40.

Kroonen J, Nassen J, Boulanger YG, Provenzano F, Capraro V, Bours V et al (2011) Human glioblastoma-initiating cells invade specifically the subventricular zones and olfactory bulbs of mice after striatal injection. Int J Cancer 129(3):574–585. https://doi.org/10.1002/ijc.25709 CrossRefPubMed

41.

Jafri NF, Clarke JL, Weinberg V, Barani IJ, Cha S (2013) Relationship of glioblastoma multiforme to the subventricular zone is associated with survival. Neuro-Oncology 15(1):91–96. https://doi.org/10.1093/neuonc/nos268 CrossRefPubMed

42.

Stark AM, van de Bergh J, Hedderich J, Mehdorn HM, Nabavi A (2012) Glioblastoma: clinical characteristics, prognostic factors and survival in 492 patients. Clin Neurol Neurosurg 114(7):840–845. https://doi.org/10.1016/j.clineuro.2012.01.026 CrossRefPubMed

43.

Lee JW, Norden AD, Ligon KL, Golby AJ, Beroukhim R, Quackenbush J et al (2014) Tumor associated seizures in glioblastomas are influenced by survival gene expression in a region-specific manner: a gene expression imaging study. Epilepsy Res 108(5):843–852. https://doi.org/10.1016/j.eplepsyres.2014.02.021 CrossRefPubMedPubMedCentral

44.

Li YM, Suki D, Hess K, Sawaya R (2015) The influence of maximum safe resection of glioblastoma on survival in 1229 patients: can we do better than gross-total resection? J Neurosurg:1–12. https://doi.org/10.3171/2015.5.JNS142087

Titel: New prognostic factor telomerase reverse transcriptase promotor mutation presents without MR imaging biomarkers in primary glioblastoma
verfasst von: Tunc F. Ersoy
Vera C. Keil
Dariusch R. Hadizadeh
Gerrit H. Gielen
Rolf Fimmers
Andreas Waha
Barbara Heidenreich
Rajiv Kumar
Hans H. Schild
Matthias Simon
Publikationsdatum: 11.09.2017
Verlag: Springer Berlin Heidelberg
Erschienen in: Neuroradiology / Ausgabe 12/2017
Print ISSN: 0028-3940
Elektronische ISSN: 1432-1920
DOI: https://doi.org/10.1007/s00234-017-1920-1

Leitlinien kompakt für die Neurologie

Mit medbee Pocketcards sicher entscheiden.

^{Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag}

Kostenlos registrieren

Neu im Fachgebiet Neurologie

23.04.2024 | Demenz | Nachrichten

Update Neurologie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.

Newsletter bestellen

Live-Webinar: Aktuelle Leitlinien bei Herz-Kreislauf-Erkrankungen

Springer Medizin

New prognostic factor telomerase reverse transcriptase promotor mutation presents without MR imaging biomarkers in primary glioblastoma

Abstract

Purpose

Methods

Results

Conclusion

Leitlinien kompakt für die Neurologie

Neu im Fachgebiet Neurologie

Demenzkranke durch Antipsychotika vielfach gefährdet

Parkinson-Therapie im Wandel – aktuelle Leitlinie im Fokus

Auf diese Krankheiten bei Geflüchteten sollten Sie vorbereitet sein

Hustenstiller lindert Agitation bei Alzheimer

Update Neurologie

Live-Webinar: Aktuelle Leitlinien bei Herz-Kreislauf-Erkrankungen

Springer Medizin

Abstract

Purpose

Methods

Results

Conclusion

Bitte loggen Sie sich ein, um Zugang zu diesem Inhalt zu erhalten

Weitere Artikel der Ausgabe 12/2017

High-resolution vessel wall MRI for the evaluation of intracranial atherosclerotic disease

Decaying molar tooth sign in Joubert syndrome and related disorders is correlated to a displacement of the corticospinal tract

European Society of Neuroradiology (ESNR)

Craniospinal fluid hypotension mimicking arteriovenous fistula on spinal MRI

In vitro, contrast agent-based evaluation of the influence of flow diverter size and position on intra-aneurysmal flow dynamics using syngo iFlow

Follow-up of pineal cysts in children: is it necessary?

Leitlinien kompakt für die Neurologie

Neu im Fachgebiet Neurologie

Demenzkranke durch Antipsychotika vielfach gefährdet

Parkinson-Therapie im Wandel – aktuelle Leitlinie im Fokus

Auf diese Krankheiten bei Geflüchteten sollten Sie vorbereitet sein

Hustenstiller lindert Agitation bei Alzheimer

Update Neurologie