OJCD  Vol.10 No.3 , September 2020
Magnetic Resonance Spectroscopy and Prognostic Analysis of Molecular Subtypes of Medulloblastoma
Yuting Zhang1, Lusheng Li2,3,4,5,6*
Abstract: Aim: The aim of this study was to investigate whether magnetic resonance spectrum (MRS) and MR imaging features can be used for non-invasive medulloblastoma subgrouping, and analyse patient characteristics and prognosis of molecular subtypes of medulloblastoma. Material and Methods: 32 patients with medulloblastoma underwent MRI prior to surgical resection, 16 of them underwent MRS. MR imaging features and metabolites measured by MRS were analysed to distinguish molecular subtypes of medulloblastoma. Patient demographics, histopathological types, and prognosis of different molecular subtypes were analysed and compared respectively. Results: MRS and MR imaging features differed from different individuals, but without statistical significance that involves acquiring non-quantitative MR imaging features and NAA/Cr, Cho/Cr, Lip/Cr, Glu and Gln/Cr ratio, to be used to determine molecular subtypes. There was no significant difference of the three molecular subtypes in age, gender and pathological type. The 5-year event-free survival (EFS) of SHH, WNT and non SHH/WNT subtype respectively were 75%, 57.1%, 38.1%, with no significant difference (p = 0.382). 5-year EFS of non SHH/WNT subtype was significantly higher in ≤3 years old group than >3 years old group (p = 0.047). Conclusion: MRS and MR imaging features can’t be used to determine molecular subtypes based on our small sample study. There was no significant difference of the prognosis in the three molecular subtypes. The prognosis of ≤3 years old group of non SHH/WNT subtype is better than >3 years old group.
Cite this paper: Zhang, Y. , Li, L. , (2020) Magnetic Resonance Spectroscopy and Prognostic Analysis of Molecular Subtypes of Medulloblastoma. Open Journal of Clinical Diagnostics, 10, 81-91. doi: 10.4236/ojcd.2020.103007.

[1]   Poretti, A., Meoded, A. and Huisman, T.A. (2012) Neuroimaging of Pediatric Posterior Fossa Tumors Including Review of the Literature. Journal of Magnetic Resonance Imaging, 35, 32-47.

[2]   Gerber, N.U., Mynarek, M., von Hoff, K., Friedrich, C., Resch, A. and Rutkowski, S. (2014) Recent Developments and Current Concepts in Medulloblastoma. Cancer Treatment Reviews, 40, 356-365.

[3]   Louis, D.N., Ohgaki, H., Wiestler, O.D., Cavenee, W.K., Burger, P.C., Jouvet, A., Scheithauer, B.W. and Kleihues, P. (2007) The 2007 WHO Classification of Tumours of the Central Nervous System. Acta Neuropathologica, 114, 97-109.

[4]   Ellison, D.W., Onilude, O.E., Lindsey, J.C., Lusher, M.E., Weston, C.L., Taylor, R.E., Pearson, A.D. and Clifford, S.C. (2005) United Kingdom Children’s Cancer Study Group Brain Tumour Committee. Beta-Catenin Status Predicts a Favorable Outcome in Childhood Medulloblastoma: The United Kingdom Children’s Cancer Study Group Brain Tumour Committee. Journal of Clinical Oncology, 23, 7951-7957.

[5]   Gajjar, A., Chintagumpala, M., Ashley, D., Kellie, S., Kun, L.E., Merchant, T.E., Woo, S., Wheeler, G., Ahern, V., Krasin, M.J., Fouladi, M., Broniscer, A., Krance, R., Hale, G.A., Stewart, C.F., Dauser, R., Sanford, R.A., Fuller, C., Lau, C., Boyett, J.M., Wallace, D. and Gilbertson, R.J. (2006) Risk-Adapted Craniospinal Radiotherapy Followed by High-Dose Chemotherapy and Stem-Cell Rescue in Children with Newly Diagnosed Medulloblastoma (St Jude Medulloblastoma-96): Long-Term Results From a Prospective, Multicentre Trial. The Lancet Oncology, 7, 813-820.

[6]   Kool, M., Korshunov, A., Remke, M., Jones, D.T., Schlanstein, M., Northcott, P.A., Cho, Y.J., Koster, J., Schouten-van Meeteren, A., van Vuurden, D., Clifford, S.C., Pietsch, T., von Bueren, A.O., Rutkowski, S., McCabe, M., Collins, V.P., Backlund, M.L., Haberler, C., Bourdeaut, F., Delattre, O., Doz, F., Ellison, D.W., Gilbertson, R.J., Pomeroy, S.L., Taylor, M.D., Lichter, P. and Pfister, S.M. (2012) Molecular Subgroups of Medulloblastoma: An International Meta-Analysis of Transcriptome, Genetic Aberrations, and Clinical Data of WNT, SHH, Group 3, and Group 4 Medulloblastomas. Acta Neuropathologica, 123, 473-484.

[7]   Northcott, P.A., Korshunov, A., Witt, H., Hielscher, T., Eberhart, C.G., Mack, S., Bouffet, E., Clifford, S.C., Hawkins, C.E., French, P., Rutka, J.T., Pfister, S. and Taylor, M.D. (2011) Medulloblastoma Comprises Four Distinct Molecular Variants. Journal of Clinical Oncology, 29, 1408-1414.

[8]   Thompson, M.C., Fuller, C., Hogg, T.L., Dalton, J., Finkelstein, D., Lau, C.C., Chintagumpala, M., Adesina, A., Ashley, D.M., Kellie, S.J., Taylor, M.D., Curran, T., Gajjar, A. and Gilbertson, R.J. (2006) Genomics Identifies Medulloblastoma Subgroups That Are Enriched for Specific Genetic Alterations. Journal of Clinical Oncology, 24, 1924-1931.

[9]   Toyooka, M., Kimura, H., Uematsu, H., Kawamura, Y., Takeuchi, H. and Itoh, H. (2008) Tissue Characterization of Glioma by Proton Magnetic Resonance Spectroscopy and Perfusion-Weighted Magnetic Resonance Imaging: Glioma Grading and Histological Correlation. Clinical Imaging, 32, 251-258.

[10]   Fayed, N., Dávila, J., Medrano, J. and Olmos, S. (2008) Malignancy Assessment of Brain Tumours with Magnetic Resonance Spectroscopy and Dynamic Susceptibility Contrast MRI. European Journal of Radiology, 67, 427-433.

[11]   Blüml, S., Margol, A.S., Sposto, R., Kennedy, R.J., Robison, N,J., Vali, M., Hung, L.T., Muthugounder, S., Finlay, J.L., Erdreich-Epstein, A., Gilles, F.H., Judkins, A.R., Krieger, M.D., Dhall, G., Nelson, M.D. and Asgharzadeh, S. (2016) Molecular Subgroups of Medulloblastoma Identification Using Noninvasive Magnetic Resonance Spectroscopy. Neuro-Oncology, 18, 126-131.

[12]   Peet, A.C., Davies, N.P., Ridley, L., Brundler, M.A., Kombogiorgas, D., Lateef, S., Natarajan, K., Sgouros, S., MacPherson, L. and Grundy, R.G. (2007) Magnetic Resonance Spectroscopy Suggests Key Differences in the Metastatic Behaviour of Medulloblastoma. European Journal of Cancer, 43, 1037-1044.

[13]   Clifford, S.C., et al. (2006) Wnt/Wingless Pathway Activation and Chromosome 6 Loss Characterize a Distinct Molecular Sub-Group of Medulloblastomas Associated with a Favorable Prognosis. Cell Cycle, 5, 2666-2670.

[14]   Pfaff, E., et al. (2010) TP53 Mutation Is Frequently Associated with CTNNB1 Mutation or MYCN Amplification and Is Compatible with Long-Term Survival in Medulloblastoma. Journal of Clinical Oncology, 28, 5188-5196.

[15]   Lindsey, J.C., et al. (2011) TP53 Mutations in Favorable-Risk Wnt/Wingless-Subtype Medulloblastomas. Journal of Clinical Oncology, 29, e344-e346.

[16]   Northcott, P.A., et al. (2011) Medulloblastoma Comprises Four Distinct Molecular Variants. Journal of Clinical Oncology, 29, 1408-1414.

[17]   Cho, Y.J., et al. (2011) Integrative Genomic Analysis of Medulloblastoma Identifies a Molecular Subgroup That Drives Poor Clinical Outcome. Journal of Clinical Oncology, 29, 1424-1430.

[18]   Taylor, M.D., Northcott, P.A., Korshunov, A., Remke, M., Cho, Y.J., Clifford, S.C., Eberhart, C.G., Parsons, D.W., Rutkowski, S., Gajjar, A., Ellison, D.W., Lichter, P., Gilbertson, R.J., Pomeroy, S.L., Kool, M. and Pfister, S.M. (2012) Molecular Subgroups of Medulloblastoma: The Current Consensus. Acta Neuropathologica, 123, 465-472.

[19]   Ellison, D.W., Kocak, M., Dalton, J., Megahed, H., Lusher, M.E., Ryan, S.L., Zhao, W., Nicholson, S.L., Taylor, R.E., Bailey, S. and Clifford, S.C. (2011) Definition of Disease-Risk Stratification Groups in Childhood Medulloblastoma Using Combined Clinical, Pathologic, and Molecular Variables. Journal of Clinical Oncology, 29, 1400-1407.

[20]   Rodriguez-Blanco, J., Pednekar, L., Penas, C., Li, B., Martin, V., Long, J., Lee, E., Weiss, W.A., Rodriguez, C., Mehrdad, N., Nguyen, D.M., Ayad, N.G., Rai, P., Capobianco, A.J. and Robbins, D.J. (2017) Inhibition of WNT Signaling Attenuates Self-Renewal of SHH-Subgroup Medulloblastoma. Oncogene, 36, 6306-6314.

[21]   Dennis, M., Spiegler, B.J., Hetherington, C.R. and Greenberg, M.L. (1996) Neuropsychological Sequelae of the Treatment of Children with Medulloblastoma. Journal of Neuro-Oncology, 29, 91-101.

[22]   Yuneva, M.O., Fan, T.W., Allen, T.D., Higashi, R.M., Ferraris, D.V., Tsukamoto, T., Matés, J.M., Alonso, F.J., Wang, C., Seo, Y., Chen, X. and Bishop, J.M. (2012) The Metabolic Profile of Tumors Depends on Both the Responsible Genetic Lesion and Tissue Type. Cell Metabolism, 15, 157-170.

[23]   Wilson, M., Cummins, C.L., Macpherson, L., Sun, Y., Natarajan, K., Grundy, R.G., Arvanitis, T.N., Kauppinen, R.A. and Peet, A.C. (2013) Magnetic Resonance Spectroscopy Metabolite Profiles Predict Survival in Paediatric Brain Tumours. European Journal of Cancer, 49, 457-464.

[24]   Marcus, K.J., Astrakas, L.G., Zurakowski, D, Zarifi, M.K., Mintzopoulos, D., Poussaint, T.Y., Anthony, D.C., De Girolami, U., Black, P.M., Tarbell, N.J. and Tzika, A.A. (2007) Predicting Survival of Children with CNS Tumors Using Proton Magnetic Resonance Spectroscopic Imaging Biomarkers. International Journal of Oncology, 30, 651-657.

[25]   Robinson, G.W. (2013) Impact of Tumor Location on Medulloblastoma Subtyping and Treatment. Pediatric Blood & Cancer, 60, 1393-1394.

[26]   Astrakas, L.G., Zurakowski, D., Tzika, A.A., Zarifi, M.K., Anthony, D.C., De Girolami, U., Tarbell, N.J. and Black, P.M. (2004) Noninvasive Magnetic Resonance Spectroscopic Imaging Biomarkers to Predict The Clinical Grade of Pediatric Brain Tumors. Clinical Cancer Research, 10, 8220-8228.

[27]   Li, X., Jin, H., Lu, Y., Oh, J., Chang, S. and Nelson, S.J. (2004) Identification of MRI and 1H MRSI Parameters That May Predict Survival for Patients with Malignant Gliomas. NMR Biomedicine, 17, 10-20.

[28]   Vaidya, S.J., Payne, G.S., Leach, M.O. and Pinkerton, C.R. (2003) Potential Role of Magnetic Resonance Spectroscopy in Assessment of Tumour Response in Childhood Cancer. European Journal of Cancer, 39, 728-735.

[29]   Wilson, M., Gill, S.K., MacPherson, L., English, M., Arvanitis, T.N. and Peet, A.C. (2014) Noninvasive Detection of Glutamate Predicts Survival in Pediatric Medulloblastoma. Clinical Cancer Research, 20, 4532-4539.

[30]   Perreault, S., Ramaswamy, V., Achrol, A.S., Chao, K., Liu, T.T., Shih, D., Remke, M., Schubert, S., Bouffet, E., Fisher, P.G., Partap, S., Vogel, H., Taylor, M.D., Cho, Y.J. and Yeom, K.W. (2014) MRI Surrogates for Molecular Subgroups of Medulloblastoma. American Journal of Neuroradiology, 35, 1263-1269.

[31]   Pietsch, T., Schmidt, R., Remke, M., Korshunov, A., Hovestadt, V., Jones, D.T., Felsberg, J., Kaulich, K., Goschzik, T., Kool, M., Northcott, P.A., von Hoff, K., von Bueren, A.O., Friedrich, C., Mynarek, M., Skladny, H., Fleischhack, G., Taylor, M.D., Cremer, F., Lichter, P., Faldum, A., Reifenberger, G., Rutkowski, S. and Pfister, S.M. (2014) Prognostic Significance of Clinical, Histopathological, and Molecular Characteristics of Medulloblastomas in the Prospective Hit2000 Multicenter Clinical Trial Cohort. Acta Neuropathologica, 128, 137-149.

[32]   Pfister, S., Remke, M., Benner, A., Mendrzyk, F., Toedt, G., Felsberg, J., Wittmann, A., Devens, F., Gerber, N.U., Joos, S., Kulozik, A., Reifenberger, G., Rutkowski, S., Wiestler, O.D., Radlwimmer, B., Scheurlen, W., Lichter, P. and Korshunov, A. (2009) Outcome Prediction in Pediatric Medulloblastoma Based on DNA Copy-Number Aberrations of Chromosomes 6q and 17q and the MYC and MYCN Loci. Journal of Clinical Oncology, 27, 1627-1636.

[33]   Rossi, A., Caracciolo, V., Russo, G., Reiss, K. and Giordano, A. (2008) Medulloblastoma: from Molecular Pathology to Therapy. Clinical Cancer Research, 14, 971-976.

[34]   Massimino, M., Biassoni, V., Gandola, L., Garrè, M.L., Gatta, G., Giangaspero, F., Poggi, G. and Rutkowski, S. (2016) Childhood Medulloblastoma. Critical Reviews in Oncology/Hematology, 105, 35-51.

[35]   Remke, M., Hielscher, T., Northcott, P.A., Witt, H., Ryzhova, M., Wittmann, A., Benner, A., von Deimling, A., Scheurlen, W., Perry, A., Croul, S., Kulozik, A.E., Lichter, P., Taylor, M.D., Pfister, S.M. and Korshunov, A. (2011) Adult Medulloblastoma Comprises Three Major Molecular Variants. Journal of Clinical Oncology, 29, 2717-2723.