Epigenetic genome-wide analysis identifies BEX1 as a candidate tumour suppressor gene in paediatric intracranial ependymoma

Cancer Letters

Volumn 346, Issue 1, 2014, Pages 34-44

  Karakoula, Katherine ^a   Jacques, Thomas S ^b,c   Phipps, Kim P ^c   Harkness, William ^c   Thompson, Dominic ^c   Harding, Brian N ^d   Darling, John L ^a   Warr, Tracy J ^a  

^a UNIVERSITY OF WOLVERHAMPTON   (United Kingdom)

^b UNIVERSITY COLLEGE LONDON   (United Kingdom)

^c GREAT ORMOND STREET HOSPITAL   (United Kingdom)

^d CHILDREN S HOSPITAL OF PHILADELPHIA   (United States)

Author keywords

5 Aza dC; BEX1; DNA methylation; Paediatric ependymoma; Pharmacological unmasking

Indexed keywords

5 AZA 2' DEOXYCYTIDINE; BISULFITE; BRAIN EXPRESSED X LINKED 1 PROTEIN; TUMOR SUPPRESSOR PROTEIN; UNCLASSIFIED DRUG;

ANTINEOPLASTIC ACTIVITY; APOPTOSIS; ARTICLE; BAI2 GENE; BEX1 GENE; CARCINOGENESIS; CCND2 GENE; CDKN2A GENE; CELL DIFFERENTIATION; CELL PROLIFERATION; CHILDHOOD INTRACRANIAL EPENDYMOMA; CLINICAL ARTICLE; COLONY FORMATION; CONTROLLED STUDY; DEMETHYLATION; DNA METHYLATION; EPENDYMOMA; EPIGENETICS; GENE; GENE EXPRESSION REGULATION; GENE FUNCTION; GENE IDENTIFICATION; GENE INACTIVATION; GENE SEQUENCE; GENE SILENCING; GENETIC ASSOCIATION; HUMAN; HUMAN CELL; HUMAN TISSUE; MICROARRAY ANALYSIS; P53 GENE; PRIORITY JOURNAL; PROMOTER REGION; QUANTITATIVE STUDY; REAL TIME POLYMERASE CHAIN REACTION; REVERSE TRANSCRIPTION POLYMERASE CHAIN REACTION; SIGNAL TRANSDUCTION; TUMOR CELL CULTURE; TUMOR SUPPRESSOR GENE; UPREGULATION; WNT GENE;

5-AZA-DC; BEX1; DNA METHYLATION; PAEDIATRIC EPENDYMOMA; PHARMACOLOGICAL UNMASKING;

BRAIN NEOPLASMS; CELLS, CULTURED; CHILD; DNA METHYLATION; EPENDYMOMA; EPIGENESIS, GENETIC; GENE EXPRESSION REGULATION, NEOPLASTIC; GENES, TUMOR SUPPRESSOR; GENOME-WIDE ASSOCIATION STUDY; HUMANS; NERVE TISSUE PROTEINS; OLIGONUCLEOTIDE ARRAY SEQUENCE ANALYSIS; REAL-TIME POLYMERASE CHAIN REACTION; TRANSFECTION;

EID: 84896713196     PISSN: 03043835     EISSN: 18727980     Source Type: Journal    
DOI: 10.1016/j.canlet.2013.12.005     Document Type: Article

References (49)

1. Kaderali Z., Lamberti-Pasculli M., Rutka J.T. The changing epidemiology of paediatric brain tumours: a review from the Hospital for Sick Children. Childs Nerv. Syst. 2009, 25:787-793.
2. Makino K., Nakamura H., Yano S., Kuratsu J. Kumamoto Brain Tumor Group, Population-based epidemiological study of primary intracranial tumors in childhood. Childs Nerv. Syst. 2010, 26:1029-1034.
3. Garvin J.H., Selch M.T., Holmes E., Berger M.S., Finlay J.L., Flannery A., Goldwein J.W., Packer R.J., Rorke-Adams L.B., Shiminski-Maher T., Sposto R., Stanley P., Tannous R., Pollack I.F., Children's Oncology Group, Phase II study of pre-irradiation chemotherapy for childhood intracranial ependymoma.Children's Cancer Group protocol 9942: a report from the Children's Oncology Group Pediatr. Blood Cancer 2012, 59:1183-1189.
4. A. Gajjar, R.J. Packer, N.K. Foreman, K. Cohen, D. Haas-Kogan, T.E. Merchant, COG Brain Tumor Committee, Children's Oncology Group's 2013 blueprint for research, Central nervous system tumors, Pediatr. Blood Cancer 60 (2013) 1022-1026.
5. Kilday J.P., Rahman R., Dyer S., Ridley L., Lowe J., Coyle B., Grundy R. Pediatric ependymoma: biological perspectives. Mol. Cancer Res. 2009, 7:765-786.
6. Carter M., Nicholson J., Ross F., Crolla J., Allibone R., Balaji V., Perry R., Walker D., Gilbertson R., Ellison D.W. Genetic abnormalities detected in ependymomas by comparative genomic hybridization. Br. J. Cancer 2002, 86:929-939.
7. Mendrzyk F., Korshunov A., Benner A., Toedt G., Pfister S., Radlwimmer B., Lichter P. Identification of gains on 1q and epidermal growth factor receptor overexpression as independent prognostic markers in intracranial ependymoma. Clin. Cancer Res. 2006, 12:2070-2079.
8. Korshunov A., Witt H., Hielscher T., Benner A., Remke M., Ryzhova M., Milde T., Bender S., Wittmann A., Schöttler A., Kulozik A.E., Witt O., von Deimling A., Lichter P., Pfister S. Molecular staging of intracranial ependymoma in children and adults. J. Clin. Oncol. 2010, 28:3182-3190.
9. Karakoula K., Suarez-Merino B., Ward S., Phipps K.P., Harkness W., Hayward R., Thompson D., Jacques T.S., Harding B., Beck J., Thomas D.G., Warr T.J. Real-time quantitative PCR analysis of pediatric ependymomas identifies novel candidate genes including TPR at 1q25 and CHIBBY at 22q12-q13. Genes Chromosomes Cancer 2008, 4:1005-1022.
10. Kilday J.P., Mitra B., Domerg C., Ward J., Andreiuolo F., Osteso-Ibanez T., Mauguen A., Varlet P., Le Deley M.C., Lowe J., Ellison D.W., Gilbertson R.J., Coyle B., Grill J., Grundy R.G. Copy number gain of 1q25 predicts poor progression-free survival for pediatric intracranial ependymomas and enables patient risk stratification: a prospective European clinical trial cohort analysis on behalf of the Children's Cancer Leukaemia Group (CCLG), Societe Francaise d'Oncologie Pediatrique (SFOP), and International Society for Pediatric Oncology (SIOP). Clin. Cancer Res. 2012, 18:2001-2011.
11. Johnson R.A., Wright K.D., Poppleton H., Mohankumar K.M., Finkelstein D., Pounds S.B., Rand V., Leary S.E., White E., Eden C., Hogg T., Northcott P., Mack S., Neale G., Wang Y.D., Coyle B., Atkinson J., DeWire M., Kranenburg T.A., Gillespie Y., Allen J.C., Merchant T., Boop F.A., Sanford R.A., Gajjar A., Ellison D.W., Taylor M.D., Grundy R.G., Gilbertson R.J. Cross-species genomics matches driver mutations and cell compartments to model ependymoma. Nature 2010, 466:632-636.
12. Jones P.A., Baylin S.B. The fundamental role of epigenetic events in cancers. Nat. Rev. Genet. 2002, 3:415-428.
13. Alonso M.E., Bello M.J., Gonzalez-Gomez P., Arjona D., Lomas J., de Campos J.M., Isla A., Sarasa J.L., Rey J.A. Aberrant promoter methylation of multiple genes in oligodendrogliomas and ependymomas. Cancer Genet. Cytogenet. 2003, 144:134-142.
14. Rousseau E., Ruchoux M.M., Scaravilli F., Chapon F., Vinchon M., De Smet C., Godfraind C., Vikkula M. CDKN2A, CDKN2B and p14ARF are frequently and differentially methylated in ependymal tumours. Neuropathol. Appl. Neurobiol. 2003, 29:574-583.
15. Waha A., Koch A., Hartmann W., Mack H., Schramm J., Sörensen N., Berthold F., Wiestler O.D., Pietsch T., Waha A. Analysis of HIC-1 methylation and transcription in human ependymomas. Int. J. Cancer 2004, 110:542-549.
16. Michalowski M.B., de Fraipont F., Michelland S., Entz-Werle N., Grill J., Pasquier B., Favrot M.C., Plantaz D. Methylation of RASSF1A and TRAIL pathway-related genes is frequent in childhood intracranial ependymomas and benign choroid plexus papilloma. Cancer Genet. Cytogenet. 2006, 166:74-81.
17. Modena P., Lualdi E., Facchinetti F., Veltman J., Reid J.F., Minardi S., Janssen I., Giangaspero F., Forni M., Finocchiaro G., Genitori L., Giordano F., Riccardi R., Schoenmakers E.F., Massimino M., Sozzi G. Identification of tumor-specific molecular signatures in intracranial ependymoma and association with clinical characteristics. J. Clin. Oncol. 2006, 24:5223-5233.
18. Rogers H.A., Kilday J.P., Mayne C., Ward J., Adamowicz-Brice M., Schwalbe E.C., Clifford S.C., Coyle B., Grundy R.G. Supratentorial and spinal pediatric ependymomas display a hypermethylated phenotype which includes the loss of tumor suppressor genes involved in the control of cell growth and death. Acta Neuropathol. 2012, 123:711-725.
19. Lodygin D., Epanchintsev A., Menssen A., Diebold J., Hermeking H. Functional epigenomics identifies genes frequently silenced in prostate cancer. Cancer Res. 2005, 65:4218-4227.
20. Ostrow K.L., Park H.L., Hoque M.O., Kim M.S., Liu J., Argani P., Westra W., Van Criekinge W., Sidransky D. Pharmacologic unmasking of epigenetically silenced genes in breast cancer. Clin. Cancer Res. 2009, 15:1184-1191.
21. Mueller W., Nutt C.L., Ehrich M., Riemenschneider M.J., von Deimling A., van den Boom D., Louis D.N. Downregulation of RUNX3 and TES by hypermethylation in glioblastoma. Oncogene 2007, 26:583-593.
22. Kleihues P., Louis D.N., Scheithauer B.W., Rorke L.B., Reifenberger G., Burger P.C., Cavenee W.K. The WHO classification of tumors of the nervous system. J. Neuropathol. Exp. Neurol. 2002, 61:215-225.
23. Lewandowicz G.M., Harding B., Harkness W., Hayward R., Thomas D.G., Darling J.L. Chemosensitivity in childhood brain tumours in vitro: evidence of differential sensitivity to lomustine (CCNU) and vincristine. Eur. J. Cancer 2002, 36:1955-1964.
24. Rowther F.B., Kardooni H., Warr T. TOUCH-UP gradient amplification method. J. Biomol. Technol. 2012, 23:1-3.
25. Suarez-Merino B., Hubank M., Revesz T., Harkness W., Hayward R., Thompson D., Darling J.L., Thomas D.G., Warr T.J. Microarray analysis of pediatric ependymoma identifies a cluster of 112 candidate genes including four transcripts at 22q12.1-q13.3. Neuro-oncology 2005, 7:20-31.
26. Foltz G., Ryu G.Y., Yoon J.G., Nelson T., Fahey J., Frakes A., Lee H., Field L., Zander K., Sibenaller Z., Ryken T.C., Vibhakar R., Hood L., Madan A. Genome-wide analysis of epigenetic silencing identifies BEX1 and BEX2 as candidate tumor suppressor genes in malignant glioma. Cancer Res. 2006, 66:6665-6674.
27. Koo J.H., Gill S., Pannell L.K., Menco B.P., Margolis J.W., Margolis F.L. The interaction of Bex and OMP reveals a dimer of OMP with a short half-life. J. Neurochem. 2004, 90:102-116.
28. Morris M.R., Ricketts C.J., Gentle D., McRonald F., Carli N., Khalili H., Brown M., Kishida T., Yao M., Banks R.E., Clarke N., Latif F., Maher E.R. Genome-wide methylation analysis identifies epigenetically inactivated candidate tumour suppressor genes in renal cell carcinoma. Oncogene 2011, 30:1390-1401.
29. Gaspar N., Grill J., Geoerger B., Lellouch-Tubiana A., Michalowski M.B., Vassal G. P53 pathway dysfunction in primary childhood ependymomas. Pediatr. Blood Cancer. 2006, 46:604-613.
30. Sharma M.C., Ghara N., Jain D., Sarkar C., Singh M., Mehta V.S. A study of proliferative markers and tumor suppressor gene proteins in different grades of ependymomas. Neuropathology 2009, 29:148-155.
31. Suzuki S.O., Iwaki T. Amplification and overexpression of mdm2 gene in ependymomas. Mod. Pathol. 2000, 13:548-553.
32. Witt H., Mack S.C., Ryzhova M., Bender S., Sill M., Isserlin R., Benner A., Hielscher T., Milde T., Remke M., Jones D.T., Northcott P.A., Garzia L., Bertrand K.C., Wittmann A., Yao Y., Roberts S.S., Massimi L., Van Meter T., Weiss W.A., Gupta N., Grajkowska W., Lach B., Cho Y.J., von Deimling A., Kulozik A.E., Witt O., Bader G.B., Hawkins C.E., Tabori U., Guha A., Rutka J.T., Lichter P., Korshunov A., Taylor M.D., Pfister S.M. Delineation of two clinically and molecularly distinct subgroups of posterior fossa ependymoma. Cancer Cell 2011, 20:143-157.
33. Vilar M., Murillo-Carretero M., Mira H., Magnusson K., Besset V., Ibáñez C.F. Bex1, anovelinteractor of the p75 neurotrophin receptor, links neurotrophin signaling to the cell cycle. EMBO J. 2006, 25:1219-1230.
34. Mukai J., Hachiya T., Shoji-Hoshino S., Kimura M.T., Nadano D., Suvanto P., Hanaoka T., Li Y., Irie S., Greene L.A., Sato T.A. NADE, a p75NTR-associated cell death executor, is involved in signal transduction mediated by the common neurotrophin receptor p75NTR. J. Biol. Chem. 2000, 275:17566-175070.
35. Becker E.B., Howell J., Kodama Y., Barker P.A., Bonni A. Characterization of the c-Jun N-terminal kinase-BimEL signaling pathway in neuronal apoptosis. J. Neurosci. 2004, 24:8762-8770.
36. Ding K., Su Y., Pang L., Lu Q., Wang Z., Zhang S., Zheng S., Mao J., Zhu Y. Inhibition of apoptosis by downregulation of hBex1, a novel mechanism, contributes to the chemoresistance of Bcr/Abl+ leukemic cells. Carcinogenesis 2009, 30:35-42.
37. Drozdov I., Svejda B., Gustafsson B.I., Mane S., Pfragner R., Kidd M., Modlin I.M. Gene network inference and biochemical assessment delineates GPCR pathways and CREB targets in small intestinal neuroendocrine neoplasia. PLoS ONE 2011, 6(8):e22457.
38. Fang X., Yoon J.G., Li L., Yu W., Shao J., Hua D., Zheng S., Hood L., Goodlett D.R., Foltz G., Lin B. The SOX2 response program in glioblastoma multiforme: an integrated ChIP-seq, expression microarray, and microRNA analysis. BMC Genomics 2011, 12:11.
39. de Ronde J.J., Lips E.H., Mulder L., Vincent A.D., Wesseling J., Nieuwland M., Kerkhoven R., Vrancken Peeters M.J., Sonke G.S., Rodenhuis S., Wessels L.F. SERPINA6, BEX1, AGTR1, SLC26A3, and LAPTM4B are markers of resistance to neoadjuvant chemotherapy in HER2-negative breast cancer. Breast Cancer Res. Treat. 2013, 137:213-223.
40. Kaur B., Cork S.M., Sandberg E.M., Devi N.S., Zhang Z., Klenotic P.A., Febbraio M., Shim H., Mao H., Tucker-Burden C., Silverstein R.L., Brat D.J., Olson J.J., Van Meir E.G. Vasculostatin inhibits intracranial glioma growth and negatively regulates in vivo angiogenesis through a CD36-dependent mechanism. Cancer Res. 2009, 69:1212-1220.
41. Kan Z., Jaiswal B.S., Stinson J., Janakiraman V., Bhatt D., Stern H.M., Yue P., Haverty P.M., Bourgon R., Zheng J., Moorhead M., Chaudhuri S., Tomsho L.P., Peters B.A., Pujara K., Cordes S., Davis D.P., Carlton V.E., Yuan W., Li L., Wang W., Eigenbrot C., Kaminker J.S., Eberhard D.A., Waring P., Schuster S.C., Modrusan Z., Zhang Z., Stokoe D., de Sauvage F.J., Faham M., Seshagiri S. Diversesomaticmutation patterns and pathway alterations in human cancers. Nature 2010, 466:869-873.
42. Sarkar R., Hunter I.A., Rajaganeshan R., Perry S.L., Guillou P., Jayne D.G. Expression of cyclin D2 is an independent predictor of the development of hepatic metastasis in colorectal cancer. Colorectal Dis. 2010, 12:316-323.
43. Hawes S.E., Stern J.E., Feng Q., Wiens L.W., Rasey J.S., Lu H., Kiviat N.B., Vesselle H. DNA hypermethylation of tumors from non-small cell lung cancer (NSCLC) patients is associated with gender and histologic type. Lung Cancer 2010, 69:172-179.
44. Herman J.G., Merlo A., Mao L., Lapidus R.G., Issa J.P., Davidson N.E., Sidransky D., Baylin S.B. Inactivation of the CDKN2/p16/MTS1 gene is frequently associated with aberrant DNA methylation in all common human cancers. Cancer Res. 1995, 55:4525-4530.
45. Jost E., Gezer D., Wilop S., Suzuki H., Herman J.G., Osieka R., Galm O. Epigenetic dysregulation of secreted Frizzled-related proteins in multiple myeloma. Cancer Lett. 2009, 281:24-31.
46. Pehlivan M., Sercan Z., Sercan H.O. SFRP1promoter methylation is associated with persistent Philadelphia chromosome in chronic myeloid leukemia. Leuk. Res. 2009, 33:1062-1067.
47. Qiu J., Ai L., Ramachandran C., Yao B., Gopalakrishnan S., Fields C.R., Delmas A.L., Dyer L.M., Melnick S.J., Yachnis A.T., Schwartz P.H., Fine H.A., Brown K.D., Robertson K.D. Invasion suppressor cystatin E/M (CST6): high-level cell type-specific expression in normal brain and epigenetic silencing in gliomas. Lab. Invest. 2008, 88:910-925.
48. Kim H.E., Symanowski J.T., Samlowski E.E., Gonzales J., Ryu B. Quantitative measurement of circulating lymphoid-specific helicase (HELLS) gene transcript: a potential serum biomarker for melanoma metastasis. Pigment Cell Melanoma Res. 2010, 23:845-848.
49. Mahner S., Baasch C., Schwarz J., Hein S., Wölber L., Jänicke F., Milde-Langosch K. C-Fos expression is a molecular predictor of progression and survival in epithelial ovarian carcinoma. Br. J. Cancer 2008, 99:1269-1275.