A Proteogenomic Approach to Understanding MYC Function in Metastatic Medulloblastoma Tumors
Abstract
:1. Introduction
2. Group 3 Medulloblastoma and c-MYC Amplification
3. Linking c-MYC Genomic Aberrations to Molecular Pathways Driving Tumor Behavior
4. Animal Models as a Platform to Understand c-MYC Function in Medulloblastoma
5. The Role of Tumor Suppressor Protein Trp53 in Group 3 Medulloblastoma
6. Advances in Proteomic Profiling of Cancers
7. Protein Quantification Using Stable Isotopic Labeling by Amino Acids in Cell Culture
8. Proteomic Analysis of Medulloblastoma and c-MYC Function
9. Characterizing Medulloblastoma Using MicroRNA–Proteomic Networks
10. Proteomic Analysis of Medulloblastoma-Derived Exosomes
11. Conclusions
Acknowledgments
Author Contributions
Conflicts of Interest
References
- Mabbott, D.J.; Spiegler, B.J.; Greenberg, M.L.; Rutka, J.T.; Hyder, D.J.; Bouffet, E. Serial evaluation of academic and behavioral outcome after treatment with cranial radiation in childhood. J. Clin. Oncol. 2005, 23, 2256–2263. [Google Scholar] [CrossRef] [PubMed]
- Cho, Y.J.; Tsherniak, A.; Tamayo, P.; Santagata, S.; Ligon, A.; Greulich, H.; Berhoukim, R.; Amani, V.; Goumnerova, L.; Eberhart, C.G.; et al. Integrative genomic analysis of medulloblastoma identifies a molecular subgroup that drives poor clinical outcome. J. Clin. Oncol. 2011, 29, 1424–1430. [Google Scholar] [CrossRef] [PubMed]
- Northcott, P.A.; Shih, D.J.; Peacock, J.; Garzia, L.; Morrissy, A.S.; Zichner, T.; Stutz, A.M.; Korshunov, A.; Reimand, J.; Schumacher, S.E.; et al. Subgroup-specific structural variation across 1000 medulloblastoma genomes. Nature 2012, 488, 49–56. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Robinson, G.; Parker, M.; Kranenburg, T.A.; Lu, C.; Chen, X.; Ding, L.; Phoenix, T.N.; Hedlund, E.; Wei, L.; Zhu, X.; et al. Novel mutations target distinct subgroups of medulloblastoma. Nature 2012, 488, 43–48. [Google Scholar] [CrossRef] [PubMed]
- Remke, M.; Hielscher, T.; Korshunov, A.; Northcott, P.A.; Bender, S.; Kool, M.; Westermann, F.; Benner, A.; Cin, H.; Ryzhova, M.; et al. FSTL5 is a marker of poor prognosis in non-WNT/non-SHH medulloblastoma. J. Clin. Oncol. 2011, 29, 3852–3861. [Google Scholar] [CrossRef] [PubMed]
- 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.; et al. Molecular subgroups of medulloblastoma: The current consensus. Acta Neuropathol. 2012, 123, 465–472. [Google Scholar] [CrossRef] [PubMed]
- Kool, M.; Jones, D.T.; Jager, N.; Northcott, P.A.; Pugh, T.J.; Hovestadt, V.; Piro, R.M.; Esparza, L.A.; Markant, S.L.; Remke, M.; et al. Genome sequencing of SHH medulloblastoma predicts genotype-related response to smoothened inhibition. Cancer Cell 2014, 25, 393–405. [Google Scholar] [CrossRef] [PubMed]
- Rudin, C.M.; Hann, C.L.; Laterra, J.; Yauch, R.L.; Callahan, C.A.; Fu, L.; Holcomb, T.; Stinson, J.; Gould, S.E.; Coleman, B.; et al. Treatment of medulloblastoma with hedgehog pathway inhibitor GDC-0449. N. Engl. J. Med. 2009, 361, 1173–1178. [Google Scholar] [CrossRef] [PubMed]
- Kool, M.; Koster, J.; Bunt, J.; Hasselt, N.E.; Lakeman, A.; van Sluis, P.; Troost, D.; Meeteren, N.S.; Caron, H.N.; Cloos, J.; et al. Integrated genomics identifies five medulloblastoma subtypes with distinct genetic profiles, pathway signatures and clinicopathological features. PLoS ONE 2008, 3, e3088. [Google Scholar] [CrossRef] [PubMed]
- Jones, D.T.; Jager, N.; Kool, M.; Zichner, T.; Hutter, B.; Sultan, M.; Cho, Y.J.; Pugh, T.J.; Hovestadt, V.; Stutz, A.M.; et al. Dissecting the genomic complexity underlying medulloblastoma. Nature 2012, 488, 100–105. [Google Scholar] [CrossRef] [PubMed]
- Pugh, T.J.; Weeraratne, S.D.; Archer, T.C.; Pomeranz Krummel, D.A.; Auclair, D.; Bochicchio, J.; Carneiro, M.O.; Carter, S.L.; Cibulskis, K.; Erlich, R.L.; et al. Medulloblastoma exome sequencing uncovers subtype-specific somatic mutations. Nature 2012, 488, 106–110. [Google Scholar] [CrossRef] [PubMed]
- Northcott, P.A.; Shih, D.J.; Remke, M.; Cho, Y.J.; Kool, M.; Hawkins, C.; Eberhart, C.G.; Dubuc, A.; Guettouche, T.; Cardentey, Y.; et al. Rapid, reliable, and reproducible molecular sub-grouping of clinical medulloblastoma samples. Acta Neuropathol. 2012, 123, 615–626. [Google Scholar] [CrossRef] [PubMed]
- Shih, D.J.; Northcott, P.A.; Remke, M.; Korshunov, A.; Ramaswamy, V.; Kool, M.; Luu, B.; Yao, Y.; Wang, X.; Dubuc, A.M.; et al. Cytogenetic prognostication within medulloblastoma subgroups. J. Clin. Oncol. 2014, 32, 886–896. [Google Scholar] [CrossRef] [PubMed]
- Roussel, M.F.; Robinson, G.W. Role of MYC in Medulloblastoma. Cold Spring Harb. Perspect. Med. 2013, 3. [Google Scholar] [CrossRef] [PubMed]
- Gibson, P.; Tong, Y.; Robinson, G.; Thompson, M.C.; Currle, D.S.; Eden, C.; Kranenburg, T.A.; Hogg, T.; Poppleton, H.; Martin, J.; et al. Subtypes of medulloblastoma have distinct developmental origins. Nature 2010, 468, 1095–1099. [Google Scholar] [CrossRef] [PubMed]
- Kawauchi, D.; Robinson, G.; Uziel, T.; Gibson, P.; Rehg, J.; Gao, C.; Finkelstein, D.; Qu, C.; Pounds, S.; Ellison, D.W.; et al. A mouse model of the most aggressive subgroup of human medulloblastoma. Cancer Cell 2012, 21, 168–180. [Google Scholar] [CrossRef] [PubMed]
- Pei, Y.; Moore, C.E.; Wang, J.; Tewari, A.K.; Eroshkin, A.; Cho, Y.J.; Witt, H.; Korshunov, A.; Read, T.A.; Sun, J.L.; et al. An animal model of MYC-driven medulloblastoma. Cancer Cell 2012, 21, 155–167. [Google Scholar] [CrossRef] [PubMed]
- Bunt, J.; Hasselt, N.E.; Zwijnenburg, D.A.; Koster, J.; Versteeg, R.; Kool, M. Joint binding of OTX2 and MYC in promotor regions is associated with high gene expression in medulloblastoma. PLoS ONE 2011, 6, e26058. [Google Scholar] [CrossRef] [PubMed]
- Adamson, D.C.; Shi, Q.; Wortham, M.; Northcott, P.A.; Di, C.; Duncan, C.G.; Li, J.; McLendon, R.E.; Bigner, D.D.; Taylor, M.D.; et al. OTX2 is critical for the maintenance and progression of Shh-independent medulloblastomas. Cancer Res. 2010, 70, 181–191. [Google Scholar] [CrossRef] [PubMed]
- Bai, R.Y.; Staedtke, V.; Lidov, H.G.; Eberhart, C.G.; Riggins, G.J. OTX2 represses myogenic and neuronal differentiation in medulloblastoma cells. Cancer Res. 2012, 72, 5988–6001. [Google Scholar] [CrossRef] [PubMed]
- Carramusa, L.; Contino, F.; Ferro, A.; Minafra, L.; Perconti, G.; Giallongo, A.; Feo, S. The PVT-1 oncogene is a MYC protein target that is overexpressed in transformed cells. J. Cell. Physiol. 2007, 213, 511–518. [Google Scholar] [CrossRef] [PubMed]
- Shtivelman, E.; Bishop, J.M. The PVT gene frequently amplifies with MYC in tumor cells. Mol. Cell. Biol. 1989, 9, 1148–1154. [Google Scholar] [CrossRef] [PubMed]
- Hill, R.M.; Kuijper, S.; Lindsey, J.C.; Petrie, K.; Schwalbe, E.C.; Barker, K.; Boult, J.K.; Williamson, D.; Ahmad, Z.; Hallsworth, A.; et al. Combined MYC and P53 defects emerge at medulloblastoma relapse and define rapidly progressive, therapeutically targetable disease. Cancer Cell 2015, 27, 72–84. [Google Scholar] [CrossRef] [PubMed]
- Poschl, J.; Stark, S.; Neumann, P.; Grobner, S.; Kawauchi, D.; Jones, D.T.; Northcott, P.A.; Lichter, P.; Pfister, S.M.; Kool, M.; et al. Genomic and transcriptomic analyses match medulloblastoma mouse models to their human counterparts. Acta Neuropathol. 2014, 128, 123–136. [Google Scholar] [CrossRef] [PubMed]
- Ramaswamy, V.; Remke, M.; Bouffet, E.; Faria, C.C.; Perreault, S.; Cho, Y.J.; Shih, D.J.; Luu, B.; Dubuc, A.M.; Northcott, P.A.; et al. Recurrence patterns across medulloblastoma subgroups: An integrated clinical and molecular analysis. Lancet Oncol. 2013, 14, 1200–1207. [Google Scholar] [CrossRef]
- Zhang, B.; Wang, J.; Wang, X.; Zhu, J.; Liu, Q.; Shi, Z.; Chambers, M.C.; Zimmerman, L.J.; Shaddox, K.F.; Kim, S.; et al. Proteogenomic characterization of human colon and rectal cancer. Nature 2014, 513, 382–387. [Google Scholar] [CrossRef] [PubMed]
- Kim, M.S.; Pinto, S.M.; Getnet, D.; Nirujogi, R.S.; Manda, S.S.; Chaerkady, R.; Madugundu, A.K.; Kelkar, D.S.; Isserlin, R.; Jain, S.; et al. A draft map of the human proteome. Nature 2014, 509, 575–581. [Google Scholar] [CrossRef] [PubMed]
- Fine, J.M.; Creyssel, R. Starch gel electrophoresis studies on abnormal proteins in myeloma and macroglobulinaemia. Nature 1959, 183, 392. [Google Scholar] [CrossRef] [PubMed]
- Hanash, S.; Taguchi, A. The grand challenge to decipher the cancer proteome. Nat. Rev. Cancer 2010, 10, 652–660. [Google Scholar] [CrossRef] [PubMed]
- Moreira, J.M.; Ohlsson, G.; Gromov, P.; Simon, R.; Sauter, G.; Celis, J.E.; Gromova, I. Bladder cancer-associated protein, a potential prognostic biomarker in human bladder cancer. Mol. Cell. Proteom. 2010, 9, 161–177. [Google Scholar] [CrossRef] [PubMed]
- Timms, J.F.; Cramer, R. Difference gel electrophoresis. Proteomics 2008, 8, 4886–4897. [Google Scholar] [CrossRef] [PubMed]
- Fujii, K.; Kondo, T.; Yamada, M.; Iwatsuki, K.; Hirohashi, S. Toward a comprehensive quantitative proteome database: Protein expression map of lymphoid neoplasms by 2-D DIGE and MS. Proteomics 2006, 6, 4856–4876. [Google Scholar] [CrossRef] [PubMed]
- Fenn, J.B.; Mann, M.; Meng, C.K.; Wong, S.F.; Whitehouse, C.M. Electrospray ionization for mass spectrometry of large biomolecules. Science 1989, 246, 64–71. [Google Scholar] [CrossRef] [PubMed]
- Branca, R.M.; Orre, L.M.; Johansson, H.J.; Granholm, V.; Huss, M.; Perez-Bercoff, A.; Forshed, J.; Kall, L.; Lehtio, J. HiRIEF LC-MS enables deep proteome coverage and unbiased proteogenomics. Nat. Methods 2014, 11, 59–62. [Google Scholar] [CrossRef] [PubMed]
- Addona, T.A.; Abbatiello, S.E.; Schilling, B.; Skates, S.J.; Mani, D.R.; Bunk, D.M.; Spiegelman, C.H.; Zimmerman, L.J.; Ham, A.J.; Keshishian, H.; et al. Multi-site assessment of the precision and reproducibility of multiple reaction monitoring-based measurements of proteins in plasma. Nat. Biotechnol. 2009, 27, 633–641. [Google Scholar] [CrossRef] [PubMed]
- Bell, A.W.; Deutsch, E.W.; Au, C.E.; Kearney, R.E.; Beavis, R.; Sechi, S.; Nilsson, T.; Bergeron, J.J.; Group, H.T.S.W. A HUPO test sample study reveals common problems in mass spectrometry-based proteomics. Nat. Methods 2009, 6, 423–430. [Google Scholar] [CrossRef] [PubMed]
- Faca, V.M.; Song, K.S.; Wang, H.; Zhang, Q.; Krasnoselsky, A.L.; Newcomb, L.F.; Plentz, R.R.; Gurumurthy, S.; Redston, M.S.; Pitteri, S.J.; et al. A mouse to human search for plasma proteome changes associated with pancreatic tumor development. PLoS Med. 2008, 5, e123. [Google Scholar] [CrossRef] [PubMed]
- Geiger, T.; Cox, J.; Ostasiewicz, P.; Wisniewski, J.R.; Mann, M. Super-SILAC mix for quantitative proteomics of human tumor tissue. Nat. Methods 2010, 7, 383–385. [Google Scholar] [CrossRef] [PubMed]
- Everley, P.A.; Krijgsveld, J.; Zetter, B.R.; Gygi, S.P. Quantitative cancer proteomics: Stable isotope labeling with amino acids in cell culture (SILAC) as a tool for prostate cancer research. Mol. Cell. Proteom. 2004, 3, 729–735. [Google Scholar] [CrossRef] [PubMed]
- Deeb, S.J.; D’Souza, R.C.; Cox, J.; Schmidt-Supprian, M.; Mann, M. Super-SILAC allows classification of diffuse large B-cell lymphoma subtypes by their protein expression profiles. Mol. Cell. Proteom. 2012, 11, 77–89. [Google Scholar] [CrossRef] [PubMed]
- Mann, M. Functional and quantitative proteomics using SILAC. Nat. Rev. Mol. Cell Biol. 2006, 7, 952–958. [Google Scholar] [CrossRef] [PubMed]
- Rajagopal, M.U.; Hathout, Y.; MacDonald, T.J.; Kieran, M.W.; Gururangan, S.; Blaney, S.M.; Phillips, P.; Packer, R.; Gordish-Dressman, H.; Rood, B.R. Proteomic profiling of cerebrospinal fluid identifies prostaglandin D2 synthase as a putative biomarker for pediatric medulloblastoma: A pediatric brain tumor consortium study. Proteomics 2011, 11, 935–943. [Google Scholar] [CrossRef] [PubMed]
- Zanini, C.; Mandili, G.; Bertin, D.; Cerutti, F.; Baci, D.; Leone, M.; Morra, I.; di Montezemolo Cordero, L.; Forni, M. Analysis of different medulloblastoma histotypes by two-dimensional gel and MALDI-TOF. Child's Nerv. Syst. 2011, 27, 2077–2085. [Google Scholar] [CrossRef] [PubMed]
- Zanini, C.; Ercole, E.; Mandili, G.; Salaroli, R.; Poli, A.; Renna, C.; Papa, V.; Cenacchi, G.; Forni, M. Medullospheres from DAOY, UW228 and ONS-76 cells: Increased stem cell population and proteomic modifications. PLoS ONE 2013, 8, e63748. [Google Scholar] [CrossRef] [PubMed]
- Anagnostopoulos, A.K.; Papathanassiou, C.; Karamolegou, K.; Anastasiadou, E.; Dimas, K.S.; Kontos, H.; Koutsopoulos, A.; Prodromou, N.; Tzortzatou-Stathopoulou, F.; Tsangaris, G.T. Proteomic studies of pediatric medulloblastoma tumors with 17p deletion. J. Proteome Res. 2015, 14, 1076–1088. [Google Scholar] [CrossRef] [PubMed]
- Saratsis, A.M.; Kambhampati, M.; Snyder, K.; Yadavilli, S.; Devaney, J.M.; Harmon, B.; Hall, J.; Raabe, E.H.; An, P.; Weingart, M.; et al. Comparative multidimensional molecular analyses of pediatric diffuse intrinsic pontine glioma reveals distinct molecular subtypes. Acta Neuropathol. 2014, 127, 881–895. [Google Scholar] [CrossRef] [PubMed]
- Staal, J.A.; Lau, L.S.; Zhang, H.; Ingram, W.J.; Hallahan, A.R.; Northcott, P.A.; Pfister, S.M.; Wechsler-Reya, R.J.; Rusert, J.M.; Taylor, M.D.; et al. Proteomic profiling of high risk medulloblastoma reveals functional biology. Oncotarget 2015, 6, 14584–14595. [Google Scholar] [CrossRef] [PubMed]
- Azizi, A.A.; Li, L.; Strobel, T.; Chen, W.Q.; Slavc, I.; Lubec, G. Identification of c-MYC-dependent proteins in the medulloblastoma cell line D425Med. Amino Acids 2012, 42, 2149–2163. [Google Scholar] [CrossRef] [PubMed]
- Dang, C.V. MYC on the path to cancer. Cell 2012, 149, 22–35. [Google Scholar] [CrossRef] [PubMed]
- Genovesi, L.A.; Anderson, D.; Carter, K.W.; Giles, K.M.; Dallas, P.B. Identification of suitable endogenous control genes for microRNA expression profiling of childhood medulloblastoma and human neural stem cells. BMC Res. Notes 2012, 5, 507. [Google Scholar] [CrossRef] [PubMed]
- Ferretti, E.; de Smaele, E.; Po, A.; di Marcotullio, L.; Tosi, E.; Espinola, M.S.; di Rocco, C.; Riccardi, R.; Giangaspero, F.; Farcomeni, A.; et al. MicroRNA profiling in human medulloblastoma. Int. J. Cancer 2009, 124, 568–577. [Google Scholar] [CrossRef] [PubMed]
- Catanzaro, G.; Besharat, Z.M.; Garg, N.; Ronci, M.; Pieroni, L.; Miele, E.; Mastronuzzi, A.; Carai, A.; Alfano, V.; Po, A.; et al. MicroRNAs-Proteomic Networks Characterizing Human Medulloblastoma-SLCs. Stem Cells Int. 2016, 2016, 2683042. [Google Scholar] [CrossRef] [PubMed]
- Mastronuzzi, A.; Miele, E.; Po, A.; Antonelli, M.; Buttarelli, F.R.; Colafati, G.S.; del Bufalo, F.; Faedda, R.; Spinelli, G.P.; Carai, A.; et al. Large cell anaplastic medulloblastoma metastatic to the scalp: Tumor and derived stem-like cells features. BMC Cancer 2014, 14, 262. [Google Scholar] [CrossRef] [PubMed]
- Constantin, L.; Constantin, M.; Wainwright, B.J. MicroRNA Biogenesis and Hedgehog-Patched Signaling Cooperate to Regulate an Important Developmental Transition in Granule Cell Development. Genetics 2016, 202, 1105–1118. [Google Scholar] [CrossRef] [PubMed]
- D'Asti, E.; Garnier, D.; Lee, T.H.; Montermini, L.; Meehan, B.; Rak, J. Oncogenic extracellular vesicles in brain tumor progression. Front. Physiol. 2012, 3, 294. [Google Scholar] [CrossRef] [PubMed]
- Al-Nedawi, K.; Meehan, B.; Micallef, J.; Lhotak, V.; May, L.; Guha, A.; Rak, J. Intercellular transfer of the oncogenic receptor EGFRvIII by microvesicles derived from tumour cells. Nat. Cell Biol. 2008, 10, 619–624. [Google Scholar] [CrossRef] [PubMed]
- Balaj, L.; Lessard, R.; Dai, L.; Cho, Y.J.; Pomeroy, S.L.; Breakefield, X.O.; Skog, J. Tumour microvesicles contain retrotransposon elements and amplified oncogene sequences. Nat. Commun. 2011, 2, 180. [Google Scholar] [CrossRef] [PubMed]
- Epple, L.M.; Griffiths, S.G.; Dechkovskaia, A.M.; Dusto, N.L.; White, J.; Ouellette, R.J.; Anchordoquy, T.J.; Bemis, L.T.; Graner, M.W. Medulloblastoma exosome proteomics yield functional roles for extracellular vesicles. PLoS ONE 2012, 7, e42064. [Google Scholar] [CrossRef] [PubMed]
- Ung, T.H.; Madsen, H.J.; Hellwinkel, J.E.; Lencioni, A.M.; Graner, M.W. Exosome proteomics reveals transcriptional regulator proteins with potential to mediate downstream pathways. Cancer Sci. 2014, 105, 1384–1392. [Google Scholar] [CrossRef] [PubMed]
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Staal, J.A.; Pei, Y.; Rood, B.R. A Proteogenomic Approach to Understanding MYC Function in Metastatic Medulloblastoma Tumors. Int. J. Mol. Sci. 2016, 17, 1744. https://doi.org/10.3390/ijms17101744
Staal JA, Pei Y, Rood BR. A Proteogenomic Approach to Understanding MYC Function in Metastatic Medulloblastoma Tumors. International Journal of Molecular Sciences. 2016; 17(10):1744. https://doi.org/10.3390/ijms17101744
Chicago/Turabian StyleStaal, Jerome A., Yanxin Pei, and Brian R. Rood. 2016. "A Proteogenomic Approach to Understanding MYC Function in Metastatic Medulloblastoma Tumors" International Journal of Molecular Sciences 17, no. 10: 1744. https://doi.org/10.3390/ijms17101744