Proteomic Profile Modification of Anaplastic Medulloblastoma after in-Vivo Radiotherapy: A Case Study
- 1 Department of Genetics, Biology and Biochemistry (MBC), University of Turin, Turin, Italy
- 2 Department of Genetics, Biology and Biochemistry (CERMS), University of Turin, Italy
- 3 Department of Genetics, Biology and Biochemistry (MBC), University of Turin, Turin, Italy
- 4 Division of Pediatric Pathology, Ospedale Infantile Regina Margherita, Turin, Italy
- 5 Department of Genetics, Biology and Biochemistry (MBC), University of Turin, Turin, Italy
- 6
Abstract
Medulloblastoma (MDB) is an aggressive tumor of Central Nervous System (CNS). Radiotherapy after radical surgery has an important role in treatment of standard and high risk patients and is followed by intensive chemotherapy. To explore modifications of protein expression induced by in vivo radiotherapy proteomic analysis was performed on a case of Anaplastic MDB. 2D-gel electrophoresis and MALDI-TOF mass spectrometry detected qualitative differences of protein expression in Anaplastic MDB at diagnosis and in relapse after radiotherapy. Relevant proteomic data were confirmed by western blot and Real-Time PCR analysis, validating the presence of Sthatmin 1 (STMN1), Heat shock protein 60 (HSP60), HSP27 and Disulfide Isomerase (ER60) among the six proteins present in both samples. The most relevant modification induced by radiotherapy was a drastic reduction of the total number of proteins (60.6%) and the appearance of few new proteins. The modifications and the striking simplification of proteins expressed by the tumor after radiotherapy may allow to tailor subsequent chemotherapy on a rational basis. A proteomic guided chemotherapy may be of great benefit to patients.
- F. Giangaspero, C. G. Eberhart, H. Haapasalo, T. Pietsch, O. D. Wiestler and D. W. Ellison, “WHO Classification of Tumors of Central Nervous System,” In: D. N. Louis, H. Ohgaki, O. D. Wiestler and W. K. Cavenee, Eds., IARC Press, Lyon, 2007, pp. 132-140.
- C. Ang, D. Hauerstock, M. C. Guiot, et al., “Characteristics and Outcome of Medulloblastoma in Adults,” Blood Cancer, Vol. 51, 2008, pp. 603-607.
- L. Riffaud, S. Saikali, E. Leray, et al., “Survival and Prognostic Factors in a Series of Adults with Medulloblastomas,” Journal of Neurosurgery, Vol. 111, 2009, pp. 478-487.
- A. Gajjar, M. Chintagumpala, D. Ashley, et al., “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,” Lancet Oncology, Vol. 7, 2006, pp. 813-820.
- A. Peyrl, K. Krapfenbauer, I. Slavc, et al., “Protein Profiles of Medulloblastoma Cell Lines DAOY and D283: Identification of Tumor-Related Proteins and Principles,” Proteomics, Vol. 3, 2003, pp. 1781-1800.
- G. Barbero, F. Carta, G. Giribaldi, et al., “Protein/RNA Coextraction and Small Twodimensional Polyacrylamide Gel Electrophoresis for Proteomic/Gene Expression Analysis of Renal Cancer Biopsies,” Analytical Biochemistry, Vol. 349, 2006, pp. 62-71.
- F. Carta, P. P. Demuro, C. Zanini, et al., “Analysis of Candidate Genes through a Proteomicsbased Approach in Primary Cell Lines from Malignant Melanomas and their Metastases,” Melanoma Research, Vol. 15, 2005, pp. 235-244.
- M. Mojsin, M. Stevanovic, “PBX1 and MEIS 1 Up-regulate SOX3gene Expression by Direct Iteraction with a Consensus Binding Site within the Basal Promoter Region,” Biochemical Journal, Vol. 425, 2009, pp. 107- 116.
- M. F. Kuo, H. S. Wang, Q. T. Kuo, et al., “High Expression of Stathmin Protein Predicts a Fulminant Course in Medulloblastoma,” Journal of Neurosurgery: Pediatrics, Vol. 4, 2009, pp. 74-80.
- C. Zanini, G. Giribaldi, G. Mandili, et al., “Inhibition of Heat Shock Proteins (HSP) Expression by Quercetin and Differential Doxorubicin Sensitization in Neuroblastoma and Ewing’s Sarcoma Cell Lines,” Journal of Neurochemistry, Vol. 103, 2007, pp. 1344-1354.
- Y. J. Qi, Q. Y. He, Y. F. Ma, et al., “Proteomic Identification of Malignant Transformation-Related Proteins in Esophageal Squamous Cell Carcinoma,” Journal of Cellular Biochemistry, Vol. 104, 2008, pp. 625-635.