Cancer stem cells in brain tumors

Stem Cells in Cancer: Should We Believe or Not?

Volumn , Issue , 2014, Pages 229-243

  De Mendoza, Fernando Hurtado ^a,b   Rodriguez, Enrique Alanya ^a,c  

^a HOSPITAL NACIONAL EDGARDO REBAGLIATI MARTINS   (Peru)

^b Perú   (Peru)

^c Centro de Oncologia Integral ALIADA   (Peru)

Author keywords

Brain tumors; Cancer stem cells; Glioblastoma; Hedhehog; Notch; Transforming growth factor; Wnt

Indexed keywords

EID: 84930985376     PISSN: None     EISSN: None     Source Type: Book    
DOI: 10.1007/978-94-017-8754-3_11     Document Type: Chapter

References (103)

1. Burningham Z, Hashibe M, Spector L, Schiffman JD (2012) The epidemiology of sarcoma. Clin Sarcoma Res 2(1):14 [Epub ahead of print]
2. Fletcher C, Unni K, Mertens F (2002) Pathology and genetics of tumors of soft tissue and bone. International Agency for Research on Cancer Press, Lyon
3. Siegel R, DeSantis C, Virgo K, Stein K, Mariotto A, Smith T et al (2012) Cancer treatment and survivorship statistics, 2012. CA Cancer J Clin 62(4):220-241. doi: 10.3322/caac.21149
4. Henderson TO, Rajaraman P, Stovall M, Constine LS, Olive A, Smith SA et al (2012) Risk factors associated with secondary sarcomas in childhood cancer survivors: a report from the childhood cancer survivor study. Int J Radiat Oncol Biol Phys 84(1):224-230
5. Valery PC, Holly EA, Sleigh AC, Williams G, Kreiger N, Bain C (2005) Hernias and Ewing's sarcoma family of tumours: a pooled analysis and meta-analysis. Lancet Oncol 6(7):485-490
6. Borden EC, Baker LH, Bell RS, Bramwell V, Demetri GD, Eisenberg BL et al (2003) Soft tissue sarcomas of adults: state of the translational science. Clin Cancer Res 9:1941-1956
7. Helman LJ, Meltzer P (2003) Mechanisms of sarcoma development. Nat Rev Cancer 3:685-694
8. Taylor BS, Barretina J, Maki RG, Antonescu CR, Singer S, Ladanyi M (2011) Advances in sarcoma genomics and new therapeutic targets. Nat Rev Cancer 11(8):541-557. doi: 10.1038/ nrc3087
9. Rodriguez R, Rubio R, Menendez P (2012) Modeling sarcomagenesis using multipotent mesenchymal stem cells. Cell Res 22(1):62-77. doi: 10.1038/cr.2011.157
10. Dominici M, Le Blanc K, Mueller I, Slaper-Cortenbach I, Marini F, Krause D et al (2006) Minimal criteria for defining multipotent mesenchymal stromal cells. The International Society for Cellular Therapy position statement. Cytotherapy 8(4):315-317
11. Lai RC, Choo A, Lim SK (2011) Derivation and characterization of human ESC-derived mesenchymal stem cells. Methods Mol Biol 698:141-150. doi: 10.1007/978-1-60761-999-4-11
12. Crisan M, Yap S, Casteilla L, Chen CW, Corselli M, Park TS et al (2008) A perivascular origin for mesenchymal stem cells in multiple human organs. Cell Stem Cell 3(3):301-313. doi: 10.1016/j.stem.2008.07.003
13. Mohseny AB, Hogendoorn PC (2011) Concise review: mesenchymal tumors: when stem cells go mad. Stem Cells 29(3):397-403. doi: 10.1002/stem.596
14. Levings PP, McGarry SV, Currie TP, Nickerson DM, McClellan S, Ghivizzani SC et al (2009) Expression of an exogenous human Oct-4 promoter identifies tumor-initiating cells in osteosarcoma. Cancer Res 69(14):5648-5655. doi: 10.1158/0008-5472.CAN-08-3580, Epub 2009 Jul 7
15. Mertens F, Antonescu CR, Hohenberger P, Ladanyi M, Modena P, D'Incalci M et al (2009) Translocation-related sarcomas. Semin Oncol 36:312-323
16. Ohali A, Avigad S, Naumov I, Goshen Y, Ash S, Yaniv I (2008) Different telomere maintenance mechanisms in alveolar and embryonal rhabdomyosarcoma. Genes Chromosomes Cancer 47(11):965-970
17. Ulaner GA, Hoffman AR, Otero J, Huang HY, Zhao Z, Mazumdar M et al (2004) Divergent patterns of telomere maintenance mechanisms among human sarcomas: sharply contrasting prevalence of the alternative lengthening of telomeres mechanism in Ewing's sarcomas and osteosarcomas. Genes Chromosomes Cancer 41(2):155-162
18. Lafferty-Whyte K, Cairney CJ, Will MB, Serakinci N, Daidone MG, Zaffaroni N et al (2009) A gene expression signature classifying telomerase and ALT immortalization reveals an hTERT regulatory network and suggests a mesenchymal stem cell origin for ALT. Oncogene 28(43):3765-3774
19. Hsu JJ, Kamath-Loeb AS, Glick E, Wallden B, Swisshelm K, Rubin BP et al (2010) Werner syndrome gene variants in human sarcomas. Mol Carcinog 49(2):166-174
20. Meyer S, Kingston H, Taylor AM, Byrd PJ, Last JI, Brennan BM et al (2004) Rhabdomyosarcoma in Nijmegen breakage syndrome: strong association with perianal primary site. Cancer Genet Cytogenet 154(2):169-174
21. Hicks MJ, Roth JR, Kozinetz CA, Wang LL (2007) Clinicopathologic features of osteosarcoma in patients with Rothmund-Thomson syndrome. J Clin Oncol 25(4):370-375
22. Stephens PJ et al (2011) Massive genomic rearrangement acquired in a single catastrophic event during cancer development. Cell 144:27-40
23. Rausch T, Jones DT, Zapatka M, Stütz AM, Zichner T, Weischenfeldt J et al (2012) Genome sequencing of pediatric medulloblastoma links catastrophic DNA rearrangements with TP53 mutations. Cell 148(1-2):59-71
24. Forment JV, Kaidi A, Jackson SP (2012) Chromothripsis and cancer: causes and consequences of chromosome shattering. Nat Rev Cancer 12(10):663-670
25. Mercado GE, Xia SJ, Zhang C, Ahn EH, Gustafson DM, Laé M et al (2008) Identification of PAX3-FKHR-regulated genes differentially expressed between alveolar and embryonal rhabdomyosarcoma: focus on MYCN as a biologically relevant target. Genes Chromosomes Cancer 47(6):510-520
26. Ayalon D, Glaser T, Werner H (2001) Transcriptional regulation of IGF-I receptor gene expression by the PAX3-FKHR oncoprotein. Growth Horm IGF Res 11(5):289-297
27. Tsuda M, Davis IJ, Argani P, Shukla N, McGill GG, Nagai M et al (2007) TFE3 fusions activate MET signaling by transcriptional up-regulation, defining another class of tumors as candidates for therapeutic MET inhibition. Cancer Res 67(3):919-929
28. Guillon N, Tirode F, Boeva V, Zynovyev A, Barillot E, Delattre O (2000) The oncogenic EWS-FLI1 protein binds in vivo GGAA microsatellite sequences with potential transcriptional activation function. PLoS One 4(3):e4932
29. Gangwal K, Sankar S, Hollenhorst PC, Kinsey M, Haroldsen SC, Shah AA et al (2008) Microsatellites as EWS/FLI response elements in Ewing's sarcoma. Proc Natl Acad Sci U S A 105(29):10149-10154
30. Boeva V, Surdez D, Guillon N, Tirode F, Fejes AP, Delattre O et al (2010) De novo motif identification improves the accuracy of predicting transcription factor binding sites in ChIPSeq data analysis. Nucleic Acids Res 38(11):e126
31. Kovar H (2010) Downstream EWS/FLI1 -upstream Ewing's sarcoma. Genome Med 2(1):8
32. Kauer M, Ban J, Kofler R, Walker B, Davis S, Meltzer P et al (2009) A molecular function map of Ewing's sarcoma. PLoS One 4(4):e5415
33. Tirode F, Laud-Duval K, Prieur A, Delorme B, Charbord P, Delattre O (2007) Mesenchymal stem cell features of Ewing tumors. Cancer Cell 11(5):421-429
34. Lessnick SL, Dacwag CS, Golub TR (2002) The Ewing's sarcoma oncoprotein EWS/FLI induces a p53-dependent growth arrest in primary human fibroblasts. Cancer Cell 1(4): 393-401
35. Richter GH, Plehm S, Fasan A, Rössler S, Unland R, Bennani-Baiti IM (2009) EZH2 is a mediator of EWS/FLI1 driven tumor growth and metastasis blocking endothelial and neuroectodermal differentiation. Proc Natl Acad Sci U S A 106:5324-5329
36. Riggi N, Suvà ML, De Vito C, Provero P, Stehle JC, Baumer K et al (2010) EWS-FLI-1 modulates miRNA145 and SOX2 expression to initiate mesenchymal stem cell reprogramming toward Ewing sarcoma cancer stem cells. Genes Dev 24:916-932
37. Fujino T, Nomura K, Ishikawa Y, Makino H, Umezawa A, Aburatani H et al (2010) Function of EWS-POU5F1 in sarcomagenesis and tumor cell maintenance. Am J Pathol 176:1973-1982
38. Yamaguchi S, Yamazaki Y, Ishikawa Y, Kawaguchi N, Mukai H, Nakamura T (2005) EWSR1 is fused to POU5F1 in a bone tumor with translocation t(6;22)(p21;q12). Genes Chromosomes Cancer 43:217-222
39. Antonescu CR, Zhang L, Chang NE, Pawel BR, Travis W, Katabi N et al (2010) EWSR1-POU5F1 fusion in soft tissue myoepithelial tumors. A molecular analysis of sixty-six cases, including soft tissue, bone, and visceral lesions, showing common involvement of the EWSR1 gene. Genes Chromosomes Cancer 49:1114-1124
40. Möller E, Stenman G, Mandahl N, Hamberg H, Mölne L, van den Oord JJ et al (2008) POU5F1, encoding a key regulator of stem cell pluripotency, is fused to EWSR1 in hidradenoma of the skin and mucoepidermoid carcinoma of the salivary glands. J Pathol 215: 78-86
41. Naka N, Takenaka S, Araki N, Miwa T, Hashimoto N, Yoshioka K et al (2010) Synovial sarcoma is a stem cell malignancy. Stem Cells 28(7):1119-1131
42. Antonescu CR, Yoshida A, Guo T, Chang NE, Zhang L, Agaram NP et al (2009) KDR activating mutations in human angiosarcomas are sensitive to specific kinase inhibitors. Cancer Res 69(18):7175-7179
43. Barretina J, Taylor BS, Banerji S, Ramos AH, Lagos-Quintana M, Decarolis PL et al (2010) Subtype-specific genomic alterations define new targets for soft-tissue sarcoma therapy. Nat Genet 42(8):715-721
44. Huang HY, Illei PB, Zhao Z, Mazumdar M, Huvos AG, Healey JH et al (2005) Ewing sarcomas with p53 mutation or p16/p14ARF homozygous deletion: a highly lethal subset associated with poor chemoresponse. J Clin Oncol 23(3):548-558
45. Gibault L, Perot G, Chibon F (2011) New insights in sarcoma oncogenesis: a comprehensive analysis of a large series of 160 soft tissue sarcomas with complex genomics. J Pathol 223:64-71
46. Daniels M, Lurkin I, Pauli R, Erbstösser E, Hildebrandt U, Hellwig K et al (2011) Spectrum of KIT/PDGFRA/BRAF mutations and Phosphatidylinositol-3-Kinase pathway gene alterations in gastrointestinal stromal tumors (GIST). Cancer Lett 312(1):43-54
47. Antonescu CR, Besmer P, Guo T, Arkun K, Hom G, Koryotowski B et al (2005) Acquired resistance to imatinib in gastrointestinal stromal tumor occurs through secondary gene mutation. Clin Cancer Res 11(11):4182-4190
48. Janeway KA, Liegl B, Harlow A, Le C, Perez-Atayde A, Kozakewich H et al (2007) Pediatric KIT wild-type and platelet-derived growth factor receptor alpha-wild-type gastrointestinal stromal tumors share KIT activation but not mechanisms of genetic progression with adult gastrointestinal stromal tumors. Cancer Res 67(19):9084-9088
49. Beroukhim R, Mermel CH, Porter D, Wei G, Raychaudhuri S, Donovan J et al (2010) The landscape of somatic copy-number alteration across human cancers. Nature 463(7283):899-905
50. Chibon F, Lagarde P, Salas S, Pérot G, Brouste V, Tirode F et al (2010) Validated prediction of clinical outcome in sarcomas and multiple types of cancer on the basis of a gene expression signature related to genome complexity. Nat Med 16(7):781-787
51. Pedeutour F, Forus A, Coindre JM, Berner JM, Nicolo G, Michiels JF et al (1999) Structure of the supernumerary ring and giant rod chromosomes in adipose tissue tumors. Genes Chromosomes Cancer 24(1):30-41
52. Sirvent N, Coindre JM, Maire G, Hostein I, Keslair F, Guillou L et al (2007) Detection of MDM2-CDK4 amplification by fluorescence in situ hybridization in 200 paraffin-embedded tumor samples: utility in diagnosing adipocytic lesions and comparison with immunohistochemistry and real-time PCR. Am J Surg Pathol 31(10):1476-1489
53. Singer S, Socci ND, Ambrosini G, Sambol E, Decarolis P, Wu Y et al (2007) Gene expression profiling of liposarcoma identifies distinct biological types/subtypes and potential therapeutic targets in well-differentiated and dedifferentiated liposarcoma. Cancer Res 67(14): 6626-6636
54. Mayr C, Hemann MT, Bartel DP (2007) Disrupting the pairing between let-7 and Hmga2 enhances oncogenic transformation. Science 315(5818):1576-1579
55. Atiye J, Wolf M, Kaur S, Monni O, Böhling T, Kivioja A et al (2005) Gene amplifications in osteosarcoma-CGH microarray analysis. Genes Chromosomes Cancer 42(2):158-163
56. Snyder EL, Sandstrom DJ, Law K, Fiore C, Sicinska E, Brito J et al (2009) c-Jun amplification and overexpression are oncogenic in liposarcoma but not always sufficient to inhibit the adipocytic differentiation programme. J Pathol 218(3):292-300
57. Chibon F, Mariani O, Derré J, Mairal A, Coindre JM, Guillou L et al (2004) ASK1 (MAP3K5) as a potential therapeutic target in malignant fibrous histiocytomas with 12q14-q15 and 6q23 amplifications. Genes Chromosomes Cancer 40(1):32-37
58. Hélias-Rodzewicz Z, Pérot G, Chibon F, Ferreira C, Lagarde P, Terrier P et al (2010) YAP1 and VGLL3, encoding two cofactors of TEAD transcription factors, are amplified and overexpressed in a subset of soft tissue sarcomas. Genes Chromosomes Cancer 49(12):1161-1171
59. Idbaih A, Coindre JM, Derré J, Mariani O, Terrier P, Ranchère D et al (2005) Myxoid malignant fibrous histiocytoma and pleomorphic liposarcoma share very similar genomic imbalances. Lab Invest 85(2):176-181
60. Gibault L, Pérot G, Chibon F, Bonnin S, Lagarde P, Terrier P et al (2011) New insights in sarcoma oncogenesis: a comprehensive analysis of a large series of 160 soft tissue sarcomas with complex genomics. J Pathol 223(1):64-71
61. Adamowicz M, Radlwimmer B, Rieker RJ, Mertens D, Schwarzbach M, Schraml P et al (2006) Frequent amplifications and abundant expression of TRIO, NKD2, and IRX2 in soft tissue sarcomas. Genes Chromosomes Cancer 45(9):829-838
62. McDermott KM, Zhang J, Holst CR, Kozakiewicz BK, Singla V, Tlsty TD (2006) p16(INK4a) prevents centrosome dysfunction and genomic instability in primary cells. PLoS Biol 4(3):e51, Epub 2006 Feb 14
63. Li H, Fan X, Kovi RC, Jo Y, Moquin B, Konz R et al (2007) Spontaneous expression of embryonic factors and p53 point mutations in aged mesenchymal stem cells: a model of agerelated tumorigenesis in mice. Cancer Res 67:10889-10898
64. Miura M, Miura Y, Padilla-Nash HM, Molinolo AA, Fu B, Patel V et al (2006) Accumulated chromosomal instability in murine bone marrow mesenchymal stem cells leads to malignant transformation. Stem Cells 24:1095-1103
65. Mohseny AB, Szuhai K, Romeo S, Buddingh EP, Briaire-de Bruijn I, de Jong D et al (2009) Osteosarcoma originates from mesenchymal stem cells in consequence of aneuploidization and genomic loss of Cdkn2. J Pathol 219:294-305
66. Tolar J, Nauta AJ, Osborn MJ, Panoskaltsis Mortari A, McElmurry RT, Bell S et al (2007) Sarcoma derived from cultured mesenchymal stem cells. Stem Cells 25:371-379
67. Rubio R, Garcia-Castro J, Gutierrez-Aranda I et al (2010) Deficiency in p53 but not retinoblastoma induces the transformation of mesenchymal stem cells in vitro and initiates leiomyosarcoma in vivo. Cancer Res 70:4185-4194
68. Danielson LS, Menendez S, Attolini CS et al (2010) A differentiation-based microRNA signature identifies leiomyosarcoma as a mesenchymal stem cell-related malignancy. Am J Pathol 177:908-917
69. Rodriguez R, Rubio R, Masip M et al (2009) Loss of p53 induces tumorigenesis in p21-deficient mesenchymal stem cells. Neoplasia 11:397-407
70. Shimizu T, Ishikawa T, Sugihara E et al (2010) c-MYC overexpression with loss of Ink4a/Arf transforms bone marrow stromal cells into osteosarcoma accompanied by loss of adipogenesis. Oncogene 29:5687-5699
71. Kirsch DG, Dinulescu DM, Miller JB et al (2007) A spatially and temporally restricted mouse model of soft tissue sarcoma. Nat Med 13:992-997
72. Tsumura H, Yoshida T, Saito H, Imanaka-Yoshida K, Suzuki N (2006) Cooperation of oncogenic K-ras and p53 deficiency in pleomorphic rhabdomyosarcoma development in adult mice. Oncogene 25:7673-7679
73. Hung SC, Yang DM, Chang CF et al (2004) Immortalization without neoplastic transformation of human mesenchymal stem cells by transduction with HPV16 E6/E7 genes. Int J Cancer 110:313-319
74. Rodriguez R, Rubio R, Gutierrez-Aranda I et al (2011) Fus-Chop fusion protein expression coupled to P53 deficiency induces liposarcoma in mouse but not human adipose-derived mesenchymal stem/stromal cells. Stem Cells 29:179-192
75. Funes JM, Quintero M, Henderson S et al (2007) Transformation of human mesenchymal stem cells increases their dependency on oxidative phosphorylation for energy production. Proc Natl Acad Sci U S A 104:6223-6228
76. Li N, Yang R, Zhang W et al (2009) Genetically transforming human mesenchymal stem cells to sarcomas: changes in cellularphenotype and multilineage differentiation potential. Cancer 115:4795-4806
77. Wild L, Funes JM, Boshoff C, Flanagan JM (2010) In vitro transformation of mesenchymal stem cells induces gradual genomic hypomethylation. Carcinogenesis 31:1854-1862
78. Hernando E, Charytonowicz E, Dudas ME et al (2007) The AKTmTOR pathway plays a critical role in the development of leiomyosarcomas. Nat Med 13:748-753
79. Wu C, Nik-Amini S, Nadesan P, Stanford WL, Alman BA (2010) Aggressive fibromatosis (desmoid tumor) is derived from mesenchymal progenitor cells. Cancer Res 70:7690-7698
80. Matushansky I, Hernando E, Socci ND et al (2007) Derivation of sarcomas from mesenchymal stem cells via inactivation of the Wnt pathway. J Clin Invest 117:3248-3257
81. Cleton-Jansen AM, Anninga JK, Briaire-de Bruijn IH et al (2009) Profiling of high-grade central osteosarcoma and its putative progenitor cells identifies tumourigenic pathways. Br J Cancer 101:1909-1918
82. Hansen MF (2002) Genetic and molecular aspects of osteosarcoma. J Musculoskelet Neuronal Interact 2(6):554-560
83. Marina N, Gebhardt M, Teot L, Gorlick R (2004) Review Biology and therapeutic advances for pediatric osteosarcoma. Oncologist 9(4):422-441
84. Sandberg AA, Bridge JA (2003) Review updates on the cytogenetics and molecular genetics of bone and soft tissue tumors: osteosarcoma and related tumors. Cancer Genet Cytogenet 145(1):1-30
85. Lewis VO (2007) Review What's new in musculoskeletal oncology. J Bone Joint Surg Am 89(6):1399-1407
86. Gibbs CP, Kukekov VG, Reith JD, Tchigrinova O, Suslov ON, Scott EW et al (2005) Stemlike cells in bone sarcomas: implications for tumorigenesis. Neoplasia 7:967-976
87. Keel SB, Jaffe KA, Petur Nielsen G, Rosenberg AE (2001) Review Orthopaedic implantrelated sarcoma: a study of twelve cases. Mod Pathol 14(10):969-977
88. Gorlick R, Anderson P, Andrulis I, Arndt C, Beardsley GP, Bernstein M et al (2003) Review Biology of childhood osteogenic sarcoma and potential targets for therapeutic development: meeting summary. Clin Cancer Res 9(15):5442-5453
89. Weatherby RP, Dahlin DC, Ivins JC (1981) Postradiation sarcoma of bone: review of 78 Mayo Clinic cases. Mayo Clin Proc 56(5):294-306
90. Haydon RC, Luu HH, He TC (2007) Osteosarcoma and osteoblastic differentiation: a new perspective on oncogenesis. Clin Orthop Relat Res 454:237-246
91. Thomas D, Kansara MJ (2006) Epigenetic modifications in osteogenic differentiation and transformation. J Cell Biochem 98(4):757-769
92. Downing JR, Head DR, Parham DM et al (1993) Detection of the (11;22)(q24;q12) translocation of Ewing's sarcoma and peripheral neuroectodermal tumor by reverse transcription polymerase chain reaction. Am J Pathol 143(5):1294-1300
93. Rodriguez-Galindo C, Spunt SL, Pappo AS (2003) Treatment of Ewing sarcoma family of tumors: current status and outlook for the future. Med Pediatr Oncol 40(5):276-287
94. Maire G, Brown CW, Bayani J et al (2008) Complex rearrangement of chromosomes 19, 21, and 22 in Ewing sarcoma involving a novel reciprocal inversion-insertion mechanism of EWS-ERG fusion gene formation: a case analysis and literature review. Cancer Genet Cytogenet 181(2):81-92
95. Sharrocks AD (2001) The ETS-domain transcription factor family. Nat Rev Mol Cell Biol 2(11):827-837
96. Tirode F, Laud-Duval K, Prieur A, Delorme B, Charbord P, Delattre O (2007) Cancer Cell 11:421-429
97. Suvà ML, Riggi N, Stehle JC, Baumer K, Tercier S, Joseph JM (2009) Identification of cancer stem cells in Ewing's sarcoma. Cancer Res 69(5):1776-1781. doi: 10.1158/0008-5472. CAN-08-2242, Epub 2009 Feb 10
98. Angwal K, Sankar S, Hollenhorst PC, Kinsey M, Haroldsen SC et al (2008) Microsatellites as EWS/FLI response elements in Ewing's sarcoma. Proc Natl Acad Sci U S A 105:10149-10154
99. Ladanyi M, Lewis R, Jhanwar SC, Gerald W, Huvos AG, Healey JH (1995) MDM2 and CDK4 gene amplification in Ewing's sarcoma. J Pathol 175:211-217
100. Kovar H, Auinger A, Jug G, Aryee D, Zoubek A et al (1993) Narrow spectrum of infrequent p53 mutations and absence of MDM2 amplification in Ewing tumours. Oncogene 8:2683-2690
101. Ban J, Bennani-Baiti IM, Kauer M, Schaefer KL, Poremba C et al (2008) EWS-FLI1 suppresses NOTCH-activated p53 in Ewing's sarcoma. Cancer Res 68:7100-7109
102. Hu-Lieskovan S, Zhang J, Wu L, Shimada H, Schofield DE, Triche TJ (2005) EWS-FLI1 fusion protein up-regulates critical genes in neural crest development and is responsible for the observed phenotype of Ewing's family of tumors. Cancer Res 65:4633-4644
103. Rorie CJ, Thomas VD, Chen P, Pierce HH, O'Bryan JP, Weissman BE (2004) The EWS/ FLI-1 fusion gene switches the differentiation program of neuroblastomas to Ewing sarcoma/ peripheral primitive neuroectodermal tumors. Cancer Res 64:1266-1277