Next-generation RNA sequencing reveals differential expression of MYCN target genes and suggests the mTOR pathway as a promising therapy target in MYCN-amplified neuroblastoma

International Journal of Cancer

Volumn 132, Issue 3, 2013, Pages

  Schramm, Alexander ^a   Köster, Johannes ^a   Marschall, Tobias ^b,c   Martin, Marcel ^c   Schwermer, Melanie ^a   Fielitz, Kathrin ^a   Büchel, Gabriele ^a   Barann, Matthias ^d   Esser, Daniela ^d   Rosenstiel, Philip ^d   Rahmann, Sven ^a,c   Eggert, Angelika ^a   Schulte, Johannes H ^a  

^a UNIVERSITY HOSPITAL ESSEN   (Germany)

^b CWI   (Netherlands)

^c TU DORTMUND UNIVERSITY   (Germany)

^d UNIVERSITY OF KIEL   (Germany)

Author keywords

mTOR pathway; MYCN; neuroblastoma; next generation sequencing

Indexed keywords

MAMMALIAN TARGET OF RAPAMYCIN; MESSENGER RNA; RNA; SMALL NUCLEOLAR RNA; TRANSCRIPTION FACTOR; TRANSCRIPTION FACTOR MYCN; TRANSCRIPTOME; UNCLASSIFIED DRUG;

ANIMAL EXPERIMENT; ARTICLE; DISEASE COURSE; DOWN REGULATION; GENE AMPLIFICATION; GENE EXPRESSION; GENE TARGETING; GENETIC IDENTIFICATION; GENETIC TRANSCRIPTION; HUMAN; HUMAN CELL; IN VITRO STUDY; IN VIVO STUDY; MOUSE; NEUROBLASTOMA; NONHUMAN; ONCOGENE MYC; PRIORITY JOURNAL; PROTEIN BINDING; PROTEIN MOTIF; PSEUDOGENE; RNA SEQUENCE; SENSITIVITY ANALYSIS; SEQUENCE ANALYSIS; UPREGULATION;

ANIMALS; CELL LINE, TUMOR; GENE EXPRESSION REGULATION, NEOPLASTIC; GENE REGULATORY NETWORKS; HIGH-THROUGHPUT NUCLEOTIDE SEQUENCING; HUMANS; MICE; NEUROBLASTOMA; NUCLEAR PROTEINS; ONCOGENE PROTEINS; PROTO-ONCOGENE PROTEINS C-MYC; RNA, MESSENGER; RNA, UNTRANSLATED; SEQUENCE ANALYSIS, RNA; TOR SERINE-THREONINE KINASES; TRANSCRIPTOME; TUMOR CELLS, CULTURED; TUMOR MARKERS, BIOLOGICAL;

EID: 84870242293     PISSN: 00207136     EISSN: 10970215     Source Type: Journal    
DOI: 10.1002/ijc.27787     Document Type: Article

References (44)

1. London WB, Castel V, Monclair T, et al. Clinical and biologic features predictive of survival after relapse of neuroblastoma: a report from the International Neuroblastoma Risk Group project. J Clin Oncol 2011; 29: 3286-92.
2. Baker DL, Schmidt ML, Cohn SL, et al. Outcome after reduced chemotherapy for intermediate-risk neuroblastoma. N Engl J Med 2010; 363: 1313-23.
3. Hero B, Simon T, Spitz R, et al. Localized infant neuroblastomas often show spontaneous regression: results of the prospective trials NB95-S and NB97. J Clin Oncol 2008; 26: 1504-10.
4. Goto S, Umehara S, Gerbing RB, et al. Histopathology (international neuroblastoma pathology classification) and MYCN status in patients with peripheral neuroblastic tumors: a report from the Children's Cancer Group. Cancer 2001; 92: 2699-708.
5. Seeger RC, Brodeur GM, Sather H, et al. Association of multiple copies of the N-myc oncogene with rapid progression of neuroblastomas. N Engl J Med 1985; 313: 1111-6.
6. Molenaar JJ, Koster J, Zwijnenburg DA, et al. Sequencing of neuroblastoma identifies chromothripsis and defects in neuritogenesis genes. Nature 2012; 483: 589-93.
7. Chen Y, Takita J, Choi YL, et al. Oncogenic mutations of ALK kinase in neuroblastoma. Nature 2008; 455: 971-4.
8. George RE, Sanda T, Hanna M, et al. Activating mutations in ALK provide a therapeutic target in neuroblastoma. Nature 2008; 455: 975-8.
9. Janoueix-Lerosey I, Lequin D, Brugieres L, et al. Somatic and germline activating mutations of the ALK kinase receptor in neuroblastoma. Nature 2008; 455: 967-70.
10. Mosse YP, Laudenslager M, Longo L, et al. Identification of ALK as a major familial neuroblastoma predisposition gene. Nature 2008; 455: 930-5.
11. Caren H, Abel F, Kogner P, et al. High incidence of DNA mutations and gene amplifications of the ALK gene in advanced sporadic neuroblastoma tumors. Biochem J 2008; 416: 153-9.
12. Mosse YP, Laudenslager M, Khazi D, et al. Germline PHOX2B mutation in hereditary neuroblastoma. Am J Hum Genet 2004; 75: 727-30.
13. van Limpt V, Schramm A, van Lakeman A, et al. The Phox2B homeobox gene is mutated in sporadic neuroblastomas. Oncogene 2004; 23: 9280-8.
14. Buckley PG, Alcock L, Bryan K, et al. Chromosomal and microRNA expression patterns reveal biologically distinct subgroups of 11q- neuroblastoma. Clin Cancer Res 2010; 16: 2971-8.
15. Caren H, Kryh H, Nethander M, et al. High-risk neuroblastoma tumors with 11q-deletion display a poor prognostic, chromosome instability phenotype with later onset. Proc Natl Acad Sci USA 2010; 107: 4323-8.
16. Schulte JH, Marschall T, Martin M, et al. Deep sequencing reveals differential expression of microRNAs in favorable versus unfavorable neuroblastoma. Nucleic Acids Res 2010; 38: 5919-28.
17. Schulte JH, Schowe B, Mestdagh P, et al. Accurate prediction of neuroblastoma outcome based on miRNA expression profiles. Int J Cancer 2010; 127: 2374-85.
18. Mestdagh P, Bostrom AK, Impens F, et al. The miR-17-92 microRNA cluster regulates multiple components of the TGF-beta pathway in neuroblastoma. Mol Cell 2010; 40: 762-73.
19. Schulte JH, Horn S, Otto T, et al. MYCN regulates oncogenic MicroRNAs in neuroblastoma. Int J Cancer 2008; 122: 699-704.
20. Ross RA, Spengler BA, Biedler JL,. Coordinate morphological and biochemical interconversion of human neuroblastoma cells. J Natl Cancer Inst 1983; 71: 741-7.
21. Schweigerer L, Breit S, Wenzel A, et al. Augmented MYCN expression advances the malignant phenotype of human neuroblastoma cells. Evidence for induction of autocrine growth activity. Cancer Res 1990; 50: 4411-6.
22. Schulte JH, Schramm A, Klein-Hitpass L, et al. Microarray analysis reveals differential gene expression patterns and regulation of single target genes contributing to the opposing phenotype of TrkA- and TrkB-expressing neuroblastomas. Oncogene 2005; 24: 165-77.
23. Klostermeier UC, Barann M, Wittig M, et al. A tissue-specific landscape of sense/antisense transcription in the mouse intestine. BMC Genom 2011; 12: 305.
24. Benjamini Y, Hochberg Y,. Controlling the false discovery rate-a practical and powerful approach to multiple testing. J R Stat Soc B Met 1995; 57: 289-300.
25. Storey JD,. A direct approach to false discovery rates. J R Stat Soc B 2002; 64: 479-98.
26. Zeller KI, Jegga AG, Aronow BJ, et al. An integrated database of genes responsive to the Myc oncogenic transcription factor: identification of direct genomic targets. Genome Biol 2003; 4: R69.
27. Murphy DM, Buckley PG, Bryan K, et al. Global MYCN transcription factor binding analysis in neuroblastoma reveals association with distinct E-box motifs and regions of DNA hypermethylation. PLoS ONE 2009; 4: e8154.
28. Marschall T, Rahmann S,. MoSDi: motif statistics and discovery. 2009. Available at http://code.google.com/p/mosdi/.
29. Weiss WA, Aldape K, Mohapatra G, et al. Targeted expression of MYCN causes neuroblastoma in transgenic mice. EMBO J 1997; 16: 2985-95.
30. Gerlinger M, Rowan AJ, Horswell S, et al. Intratumor heterogeneity and branched evolution revealed by multiregion sequencing. N Engl J Med 2012; 366: 883-92.
31. Parsons DW, Li M, Zhang X, et al. The genetic landscape of the childhood cancer medulloblastoma. Science 2011; 331: 435-9.
32. Zhang J, Benavente CA, McEvoy J, et al. A novel retinoblastoma therapy from genomic and epigenetic analyses. Nature 2012; 481: 329-34.
33. Mestdagh P, Fredlund E, Pattyn F, et al. MYCN/c-MYC-induced microRNAs repress coding gene networks associated with poor outcome in MYCN/c-MYC-activated tumors. Oncogene 2010; 29: 1394-404.
34. Wei JS, Song YK, Durinck S, et al. The MYCN oncogene is a direct target of miR-34a. Oncogene 2008; 27: 5204-13.
35. Bernard D, Prasanth KV, Tripathi V, et al. A long nuclear-retained non-coding RNA regulates synaptogenesis by modulating gene expression. EMBO J 2010; 29: 3082-93.
36. Kogo R, Shimamura T, Mimori K, et al. Long noncoding RNA HOTAIR regulates polycomb-dependent chromatin modification and is associated with poor prognosis in colorectal cancers. Cancer Res 2011; 71: 6320-6.
37. Niinuma T, Suzuki H, Nojima M, et al. Upregulation of miR-196a and HOTAIR drive malignant character in gastrointestinal stromal tumors. Cancer Res 2012; 72: 1126-36.
38. Schramm A, Schulte JH, Klein-Hitpass L, et al. Prediction of clinical outcome and biological characterization of neuroblastoma by expression profiling. Oncogene 2005; 24: 7902-12.
39. Guo X, Chen QR, Song YK, et al. Exon array analysis reveals neuroblastoma tumors have distinct alternative splicing patterns according to stage and MYCN amplification status. BMC Med Genom 2011; 4: 35.
40. Qing G, Skuli N, Mayes PA, et al. Combinatorial regulation of neuroblastoma tumor progression by N-Myc and hypoxia inducible factor HIF-1alpha. Cancer Res 2010; 70: 10351-61.
41. Boon K, Caron HN, van Asperen R, et al. N-myc enhances the expression of a large set of genes functioning in ribosome biogenesis and protein synthesis. EMBO J 2001; 20: 1383-93.
42. Krasnoselsky AL, Whiteford CC, Wei JS, et al. Altered expression of cell cycle genes distinguishes aggressive neuroblastoma. Oncogene 2005; 24: 1533-41.
43. Johnsen JI, Segerstrom L, Orrego A, et al. Inhibitors of mammalian target of rapamycin downregulate MYCN protein expression and inhibit neuroblastoma growth in vitro and in vivo. Oncogene 2008; 27: 2910-22.
44. Segerstrom L, Baryawno N, Sveinbjornsson B, et al. Effects of small molecule inhibitors of PI3K/Akt/mTOR signaling on neuroblastoma growth in vitro and in vivo. Int J Cancer 2011; 129: 2958-65.