Abstract
Genetic studies can help in diagnosis, prognosis and treatment of pediatric bone sarcoma patients. On the basis of recent discoveries, new drugs (targeted therapies) to help cure these patients are being developed.
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Referenes
Clark JC, Dass CR, Choong PF. A review of clinical and molecular prognostic factors in osteosarcoma. J Cancer Res Clin Oncol. 2008;134:281ā297.
Ek ET, Ojaimi J, Kitagawa Y, Choong PF. Does the degree of intratumoral microvessel density and VEGF expression have prognostic significance in osteosarcoma. Oncol Rep. 2006;16:17ā23.
Kreuter M, Bieker R, Bielack SS, Prognostic relevance of increased angiogenesis in osteosarcoma. Clin Cancer Res. 2004;10:8531ā8537.
Stempak D, Gammon J, Halton J, Moghrabi A, Koren G, Baruchel S. A pilot pharmacokinetic and antiangiogenic biomarker study of celecoxib and low-dose metronomic vinblastine or cyclophosphamide in pediatric recurrent solid tumors. J Pediatr Hematol Oncol. 2006;28:720ā728.
Foukas AF, Deshmukh NS, Grimer RJ, Mangham DC, Mangos EG, Taylor S. Stage-IIB osteosarcomas around the knee A study of MMP-9 in surviving tumor cells. J Bone Joint Surg Br. 2002;84:706ā711.
Kido A, Tsutsumi M, Iki K, Overexpression of matrix metalloproteinase (MMP)-9 correlates with metastatic potency of spontaneous and 4-hydroxyaminoquinoline 1-oxide (4-HAQO)-induced transplantable osteosarcomas in rats. Cancer Lett. 1999;137:209ā216.
Pakos EE, Ioannidis JP. The association of P-glycoprotein with response to chemotherapy and clinical outcome in patients with osteosarcoma A meta-analysis. Cancer. 2003 August 1;98(3):581ā589.
Baldini N, Scotlandi K, Serra M, P-glycoprotein expression in osteosarcoma: a basis for risk-adapted adjuvant chemotherapy. J Orthop Res. 1999;17:629ā632.
Park YB, Kim HS, Oh JH, Lee SH. The co-expression of p53 protein and P-glycoprotein is correlated to a poor prognosis in osteosarcoma. Int Orthop. 2001;24:307ā310.
Kansara M, Thomas DM. Molecular pathogenesis of osteosarcoma. DNA Cell Biol. 2007;26:1ā18.
Soussi T, Leblanc T, Baruchel A, Schaison G. Germline mutations of the p53 tumor-suppressor gene in cancer-prone families: a review. Nouv Rev Fr Hematol. 1993;35:33ā36.
Kaseta MK, Khaldi L, Gomatos IP, Prognostic value of bax, bcl-2, and p53 staining in primary osteosarcoma. J Surg Oncol. 2008;97:259ā266.
Wunder JS, Gokgoz N, Parkes R, TP53 mutations and outcome in osteosarcoma: a prospective, multicenter study. J Clin Oncol. 2005;23:1483ā1490.
Belchis DA, Gocke CD, Geradts J. Alterations in the rb, p16, and cyclin d1 cell cycle control pathway in osteosarcomas. Pediat Pathol Mol Med. 2000;19:377ā389.
Yamaguchi T, Toguchida J, Yamamuro T, Allelotype analysis in osteosarcomas: frequent allele loss on 3q, 13q, 17p, and 18q. Cancer Res. 1992;52:2419ā2423.
Wadayama B, Feugeas O, Guriec N, Loss of heterozygosity of the RB gene is a poor prognostic factor in patients with osteosarcoma. J Clin Oncol. 1996;14:467ā472.
Benassi MS, Molendini L, Gamberi G, Alteration of pRb/p16/cdk4 regulation in human osteosarcoma. Int J Cancer. 1999;84:489ā493.
Miller CW, Aslo A, Won A, Tan M, Lampkin B, Koeffler HP. Alterations of the p53, Rb and MDM2 genes in osteosarcoma. J Cancer Res Clin Oncol. 1996;122:559ā565.
Wadayama B, Toguchida J, Shimizu T, Mutation spectrum of the retinoblastoma gene in osteosarcomas. Cancer Res. 1994;54:3042ā3048.
PatiƱo-GarcĆa A, PiƱeiro ES, DĆez MZ, Iturriagagoitia LG, KlĆ¼ssmann FA, Ariznabarreta LS. Genetic and epigenetic alterations of the cell cycle regulators and tumor suppressor genes in pediatric osteosarcomas. J Pediatr Hematol Oncol. 2003;25:362ā367.
Wunder JS, Czitrom AA, Kandel R, Andrulis IL. Analysis of alterations in the retinoblastoma gene and tumor grade in bone and soft-tissue sarcomas. J Natl Cancer Inst. 1991;83:194ā200.
Heinsohn S, Evermann U, Zur Stadt U, Bielack S, Kabisch H. Determination of the prognostic value of loss of heterozygosity at the retinoblastoma gene in osteosarcoma. Int J Oncol. 2007;30:1205ā1214.
Chen K, Fallen S, Abaan HO, Hayran M, WNT10b induces chemotaxis of osteosarcoma and correlates with reduced survival. Pediatr Blood Cancer. 2008;51:349ā355.
Hoang BH, Kubo T, Healey JH, Expression of LDL receptor-related protein 5 (LRP5) as a novel marker for disease progression in high-grade osteosarcoma. Int J Cancer. 2004; 109:106ā111.
Rakesh Kumar V, Gupta N, Kakkar N, Sharma SC. Prognostic and predictive value of c-erbB2 overexpression in osteogenic sarcoma. J Cancer Res Ther. 2006;2:20ā23.
Zhou H, Randall RL, Brothman AR, Maxwell T, Coffin CM, Goldsby RE. Her-2/neu expression in osteosarcoma increases risk of lung metastasis and can be associated with gene amplification. J Pediatr Hematol Oncol. 2003;25:27ā32.
Ferrari S, Zanella L, Alberghini M, Palmerini E, Staals E, Bacchini P. Prognostic significance of immunohistochemical expression of ezrin in non-metastatic high-grade osteosarcoma. Pediatr Blood Cancer. 2008;50:752ā756.
Park HR, Jung WW, Bacchini P, Bertoni F, Kim YW, Park YK. Ezrin in osteosarcoma: comparison between conventional high-grade and central low-grade osteosarcoma. Pathol Res Pract. 2006;202:509ā515.
Chavez Kappel C, Velez-Yanguas C, Hirschfeld S, Helman LJ. Human osteosarcoma cell lines are dependent on insulin-like growth factor for in vitro growth. Cancer Res. 1994; 54:2803ā2807.
Rodriguez-Galindo C, Poquette CA, Daw NC, Tan M, Meyer WH, and Cleveland JL. Circulating concentrations of IGF-I and IGFBP-3 are not predictive of incidence or clinical behavior of pediatric osteosarcoma. Med Pediatr Oncol. 2001;36:605ā611.
Sandberg AA, Bridge JA. Updates on the cytogenetics and molecular genetics of bone and soft tissue tumors: osteosarcoma and related tumors. Cancer Genet Cytogenet. 2003;145:1ā30.
Squire JA, Pei J, Marrano P, High-resolution mapping of amplifications and deletions in pediatric osteosarcoma by use of CGH analysis of cDNA microarrays. Genes Chromosomes Cancer. 2003;38:215ā225.
Forus A, Weghuis DO, Smeets D, Fodstad O, Myklebost O, Geurts van Kessel A. Comparative genomic hybridization analysis of human sarcomas: II. Identification of novel amplicons at 6p and 17p in osteosarcomas. Genes Chromosomes Cancer. 1995;14:15ā21.
Tarkkanen M, Karhu R, Kallioniemi A, Gains and losses of DNA sequences in osteosarcomas by comparative genomic hybridization. Cancer Res. 1995;55:1334ā1338.
Zielenska M, Marrano P, Thorner P, High-resolution cDNA microarray CGH mapping of genomic imbalances in osteosarcoma using formalin-fixed paraffin-embedded tissue. Cytogenet Genome Res. 2004;107:77ā82.
Ozaki T, Schaefer KL, Wai D, Genetic imbalances revealed by comparative genomic hybridization in osteosarcomas. Int J Cancer. 2002;102:355ā365.
Gurney JG, Davis S, Severson RK, Fang JY, Ross JA, Robison LL. Trends in cancer incidence among children in the U.S. Cancer. 1996;78:532ā541.
Arndt CA, Crist WM. Common musculoskeletal tumors of childhood and adolescence. N Engl J Med. 1999;341:342ā352.
de Alava E, Gerald WL. Molecular biology of the Ewingās sarcoma/primitive neuroectodermal tumor family. J Clin Oncol. 2000;18:204ā213.
Grier HE. The Ewing family of tumors Ewingās sarcoma and primitive neuroectodermal tumors. Pediatr Clin North Am. 1997;44:991ā1004.
Franchi A, Pasquinelli G, Cenacchi G, Immunohistochemical and ultrastructural investigation of neural differentiation in Ewing sarcoma/PNET of bone and soft tissues. Ultrastruct Pathol. 2001;25:219ā225.
Kovar H, Dworzak M, Strehl S, Overexpression of the pseudoautosomal gene MIC2 in Ewingās sarcoma and peripheral primitive neuroectodermal tumor. Oncogene. 1990;5:1067ā1070.
Ushigome SMR, Sorensen PH. Ewing sarcoma/Primitive neuroectodermal tumor (PNET). In: Christopher DM, Fletcher KKU, Fredrik M, eds. Pathology and Genetics of Tumors of Soft Tissue and BoneWorld Health Organization Classification of Tumors. Lyon: Pathology and Genetics of Tumors of Soft Tissue and Bone International Agency for Research on Cancer; 2002.
Peter M, Gilbert E, Delattre O. A multiplex real-time PCR assay for the detection of gene fusions observed in solid tumors. Lab Invest. 2001;81:905ā912.
Burchill SA. Ewingās sarcoma: diagnostic, prognostic, and therapeutic implications of molecular abnormalities. J Clin Pathol. 2003;56:96ā102.
Paulussen M, Ahrens S, Craft AW, Ewingās tumors with primary lung metastases: survival analysis of 114 (European Intergroup) Cooperative Ewingās Sarcoma Studies patients. J Clin Oncol. 1998;16:3044ā3052.
Cotterill SJ, Ahrens S, Paulussen M, Prognostic factors in Ewingās tumor of bone: analysis of 975 patients from the European Intergroup Cooperative Ewingās Sarcoma Study Group. J Clin Oncol. 2000;18:3108ā114.
Mackall CL, Meltzer PS, Helman LJ. Focus on sarcomas. Cancer Cell. 2002;2:175ā178.
Delattre O, Zucman J, Plougastel B, Gene fusion with an ETS DNA-binding domain caused by chromosome translocation in human tumors. Nature. 1992;359:162ā165.
de Alava E, Kawai A, Healey JH, EWS-FLI1 fusion transcript structure is an independent determinant of prognosis in Ewingās sarcoma. J Clin Oncol. 1998;16:1248ā1255.
Zoubek A, Dockhorn-Dworniczak B, Delattre O, Does expression of different EWS chimeric transcripts define clinically distinct risk groups of Ewing tumor patients. J. Clin Oncol. 1996;14:1245ā1251.
Ben-David Y, Giddens EB, Letwin K, Bernstein A. Erythroleukemia induction by Friend murine leukemia virus: insertional activation of a new member of the ets gene family, Fli-1, closely linked to c-ets-1. Genes Dev. 1991;5:908ā918.
Melet F, Motro B, Rossi DJ, Zhang L, Bernstein A. Generation of a novel Fli-1 protein by gene targeting leads to a defect in thymus development and a delay in Friend virus-induced erythroleukemia. Mol Cell Biol. 1996;16:2708ā2718.
Ohno T, Ouchida M, Lee L, Gatalica Z, Rao VN, Reddy ES. The EWS gene, involved in Ewing family of tumors, malignant melanoma of soft parts and desmoplastic small round cell tumors, codes for an RNA binding protein with novel regulatory domains. Oncogene. 1994;9:3087ā3097.
Bertolotti A, Lutz Y, Heard DJ, Chambon P, Tora L. hTAF(II)68, a novel RNA/ssDNA-binding protein with homology to the pro-oncoproteins TLS/FUS and EWS is associated with both TFIID and RNA polymerase II. EMBO J. 1996;15:5022ā5031.
Aman P, Panagopoulos I, Lassen C, Expression patterns of the human sarcoma-associated genes FUS and EWS and the genomic structure of FUS. Genomics. 1996;37:1ā8.
Shing DC, McMullan DJ, Roberts P, FUS/ERG gene fusions in Ewingās tumors. Cancer Res. 2003;63:4568ā4576.
Crozat A, Aman P, Mandahl N, Ron D. Fusion of CHOP to a novel RNA-binding protein in human myxoid liposarcoma. Nature. 1993;363:640ā644.
Labelle Y, Zucman J, Stenman G, Oncogenic conversion of a novel orphan nuclear receptor by chromosome translocation. Hum Mol Genet. 1995;4:2219ā2226.
Ladanyi M, Gerald W. Fusion of the EWS and WT1 genes in the desmoplastic small round cell tumor. Cancer Res. 1994;54:2837ā2840.
Petermann R, Mossier BM, Aryee DN, Khazak V, Golemis EA, Kovar H. Oncogenic EWS-Fli1 interacts with hsRPB7, a subunit of human RNA polymerase II. Oncogene. 1998;17:603ā610.
Yang L, Chansky HA, Hickstein DD. EWS.Fli-1 fusion protein interacts with hyperphosphorylated RNA polymerase II and interferes with serine-arginine protein-mediated RNA splicing. J Biol Chem. 2000;275:37612ā37618.
Knoop LL, Baker SJ. The splicing factor U1C represses EWS/FLI-mediated transactivation. J Biol Chem. 2000;275:24865ā24871.
Knoop LL, Baker SJ. EWS/FLI alters 5āā²-splice site selection. J Biol Chem. 2001; 276:22317ā22322.
Spahn L, Petermann R, Siligan C, Schmid JA, Aryee DN, Kovar H. Interaction of the EWS NH2 terminus with BARD1 links the Ewingās sarcoma gene to a common tumor suppressor pathway. Cancer Res. 2002;62:4583ā4587.
May WA, Gishizky ML, Lessnick SL, Ewing sarcoma 11;22 translocation produces a chimeric transcription factor that requires the DNA-binding domain encoded by FLI1 for transformation. Proc Natl Acad Sci U S A. 1993;90:5752ā5756.
Lessnick SL, Braun BS, Denny CT, May WA. Multiple domains mediate transformation by the Ewingās sarcoma EWS/FLI-1 fusion gene. Oncogene. 1995;10:423ā431.
Janknecht R, Nordheim A. Gene regulation by Ets proteins. Biochim Biophys Acta. 1993;1155:346ā356.
Huang HY, Illei PB, Zhao Z, Ewing sarcomas with p53 mutation or p16/p14ARF homozygous deletion: a highly lethal subset associated with poor chemoresponse. J Clin Oncol. 2005;23:548ā558.
Zucman J, Melot T, Desmaze C, Combinatorial generation of variable fusion proteins in the Ewing family of tumors. EMBO J. 1993;12:4481ā4487.
Jeon IS, Davis JN, Braun BS, A variant Ewingās sarcoma translocation (7;22) fuses the EWS gene to the ETS gene ETV1. Oncogene. 1995;10:1229ā1234.
Kaneko Y, Yoshida K, Handa M, Fusion of an ETS-family gene, EIAF, to EWS by t(17;22)(q12;q12) chromosome translocation in an undifferentiated sarcoma of infancy. Genes Chromosomes Cancer. 1996;15:115ā121.
Peter M, Couturier J, Pacquement H, A new member of the ETS family fused to EWS in Ewing tumors. Oncogene. 1997;14:1159ā1164.
Torchia EC, Jaishankar S, Baker SJ. Ewing tumor fusion proteins block the differentiation of pluripotent marrow stromal cells. Cancer Res. 2003;63:3464ā3468.
Gonzalez I, Vicent S, de Alava E, Lecanda F. EWS/FLI-1 oncoprotein subtypes impose different requirements for transformation and metastatic activity in a murine model. J Mol Med. 2007;85:1015ā1029.
Gershon TR, Oppenheimer O, Chin SS, Gerald WL. Temporally regulated neural crest transcription factors distinguish neuroectodermal tumors of varying malignancy and differentiation. Neoplasia. 2005;7:575ā584.
Teitell MA, Thompson AD, Sorensen PH, Shimada H, Triche TJ, Denny CT. EWS/ETS fusion genes induce epithelial and neuroectodermal differentiation in NIH 3T3 fibroblasts. Lab Invest. 1999;79:1535ā1543.
Rorie CJ, Thomas VD, Chen P, Pierce HH, OāBryan JP, Weissman BE. The Ews/Fli-1 fusion gene switches the differentiation program of neuroblastomas to Ewing sarcoma/peripheral primitive neuroectodermal tumors. Cancer Res. 2004;64:1266ā1277.
Hu-Lieskovan S, Zhang J, Wu L, Shimada H, Schofield DE, Triche TJ. EWS-FLI1 fusion protein up-regulates critical genes in neural crest development and is responsible for the observed phenotype of Ewingās family of tumors. Cancer Res. 2005;65:4633ā4644.
Deneen B, Denny CT. Loss of p16 pathways stabilizes EWS/FLI1 expression and complements EWS/FLI1 mediated transformation. Oncogene. 2001;20:6731ā6741.
Castillero-Trejo Y, Eliazer S, Xiang L, Richardson JA, Ilaria RL, Jr. Expression of the EWS/FLI-1 oncogene in murine primary bone-derived cells results in EWS/FLI-1-dependent, Ewing sarcoma-like tumors. Cancer Res. 2005;65:8698ā8705.
Riggi N, Cironi L, Provero P, Development of Ewingās sarcoma from primary bone marrow-derived mesenchymal progenitor cells. Cancer Res. 2005;65:11459ā11468.
Tolar J, Nauta AJ, Osborn MJ, Sarcoma derived from cultured mesenchymal stem cells. Stem Cells. 2007;25:371ā379.
Rangarajan A, Hong SJ, Gifford A, Weinberg RA. Species- and cell type-specific requirements for cellular transformation. Cancer Cell. 2004;6:171ā183.
Riggi N, Suva ML, Suva D, EWS-FLI-1 expression triggers a Ewingās sarcoma initiation program in primary human mesenchymal stem cells. Cancer Res. 2008;68:2176ā2185.
Tirode F, Laud-Duval K, Prieur A, Delorme B, Charbord P, Delattre O. Mesenchymal stem cell features of Ewing tumors. Cancer Cell. 2007;11:421ā429.
Szuhai K, Ijszenga M, Tanke HJ, Rosenberg C, Hogendoorn PC. Molecular cytogenetic characterization of four previously established and two newly established Ewing sarcoma cell lines. Cancer Genet Cytogenet. 2006;166:173ā179.
Kovar H, Jug G, Aryee DN, Among genes involved in the RB dependent cell cycle regulatory cascade, the p16 tumor suppressor gene is frequently lost in the Ewing family of tumors. Oncogene. 1997;15:2225ā2232.
Tsuchiya T, Sekine K, Hinohara S, Namiki T, Nobori T, Kaneko Y. Analysis of the p16INK4, p14ARF, p15, TP53, and MDM2 genes and their prognostic implications in osteosarcoma and Ewing sarcoma. Cancer Genet Cytogenet. 2000;120:91ā98.
Lopez-Guerrero JA, Pellin A, Noguera R, Carda C, Llombart-Bosch A. Molecular analysis of the 9p21 locus and p53 genes in Ewing family tumors. Lab Invest. 2001;81:803ā814.
Bonnet D, Dick JE. Human acute myeloid leukemia is organized as a hierarchy that originates from a primitive hematopoietic cell. Nat Med. 1997;3:730ā737.
Jamieson CH, Weissman IL, Passegue E. Chronic versus acute myelogenous leukemia: a question of self-renewal. Cancer Cell. 2004;6:531ā533.
Smith R, Owen LA, Trem DJ, Expression profiling of EWS/FLI identifies NKX2.2 as a critical target gene in Ewingās sarcoma. Cancer Cell. 2006;9:405ā416.
Owen LA, Kowalewski AA, Lessnick SL. EWS/FLI mediates transcriptional repression via NKX2.2 during oncogenic transformation in Ewingās sarcoma. PLoS ONE. 2008;3:e1965.
Fukuma M, Okita H, Hata J, Umezawa A. Upregulation of Id2, an oncogenic helix-loop-helix protein, is mediated by the chimeric EWS/ets protein in Ewing sarcoma. Oncogene. 2003;22:1ā9.
Nishimori H, Sasaki Y, Yoshida K, The Id2 gene is a novel target of transcriptional activation by EWS-ETS fusion proteins in Ewing family tumors. Oncogene. 2002;21:8302ā8309.
Zwerner JP, May WA. PDGF-C is an EWS/FLI induced transforming growth factor in Ewing family tumors. Oncogene. 2001;20:626ā633.
Matsumoto Y, Tanaka K, Nakatani F, Matsunobu T, Matsuda S, Iwamoto Y. Downregulation and forced expression of EWS-Fli1 fusion gene results in changes in the expression of G(1)regulatory genes. Br J Cancer. 2001;84:768ā775.
Wai DH, Schaefer KL, Schramm A, Expression analysis of pediatric solid tumor cell lines using oligonucleotide microarrays. Int J Oncol. 2002;20:441ā451.
Dauphinot L, De Oliveira C, Melot T, Analysis of the expression of cell cycle regulators in Ewing cell lines: EWS-FLI-1 modulates p57KIP2and c-Myc expression. Oncogene. 2001;20:3258ā3265.
Bailly RA, Bosselut R, Zucman J, DNA-binding and transcriptional activation properties of the EWS-FLI-1 fusion protein resulting from the t(11;22) translocation in Ewing sarcoma. Mol Cell Biol. 1994;14:3230ā3241.
Takahashi A, Higashino F, Aoyagi M, EWS/ETS fusions activate telomerase in Ewingās tumors. Cancer Res. 2003;63:8338ā8344.
Nakatani F, Tanaka K, Sakimura R, Identification of p21WAF1/CIP1 as a direct target of EWS-Fli1 oncogenic fusion protein. J Biol Chem. 2003;278:15105ā15115.
Hahm KB. Repression of the gene encoding the TGF-beta type II receptor is a major target of the EWS-FLI1 oncoprotein. Nat Genet. 1999;23:481.
Im YH, Kim HT, Lee C, EWS-FLI1, EWS-ERG, and EWS-ETV1 oncoproteins of Ewing tumor family all suppress transcription of transforming growth factor beta type II receptor gene. Cancer Res. 2000;60:1536ā1540.
Prieur A, Tirode F, Cohen P, Delattre O. EWS/FLI-1 silencing and gene profiling of Ewing cells reveal downstream oncogenic pathways and a crucial role for repression of insulin-like growth factor binding protein 3. Mol Cell Biol. 2004;24:7275ā7283.
Scotlandi K, Benini S, Nanni P, Blockage of insulin-like growth factor-I receptor inhibits the growth of Ewingās sarcoma in athymic mice. Cancer Res. 1998;58:4127ā4131.
Scotlandi K, Avnet S, Benini S, Expression of an IGF-I receptor dominant negative mutant induces apoptosis, inhibits tumorigenesis and enhances chemosensitivity in Ewingās sarcoma cells. Int J Cancer. 2002;101:11ā16.
Scotlandi K, Maini C, Manara MC, Effectiveness of insulin-like growth factor I receptor antisense strategy against Ewingās sarcoma cells. Cancer Gene Ther. 2002;9:296ā307.
Manara MC, Landuzzi L, Nanni P, Preclinical in vivo study of new insulin-like growth factor-I receptor-specific inhibitor in Ewingās sarcoma. Clin Cancer Res. 2007;13:1322ā1330.
Kinsey M, Smith R, Lessnick SL. NR0B1 is required for the oncogenic phenotype mediated by EWS/FLI in Ewingās sarcoma. Mol Cancer Res. 2006;4:851ā859.
112. Garcia-Aragoncillo E, Carrillo J, Lalli E, et al. DAX1, a direct target of EWS/FLI1 oncoprotein, is a principal regulator of cell-cycle progression in Ewingās tumor cells. Oncogene. 2008.
Mendiola M, Carrillo J, Garcia E, The orphan nuclear receptor DAX1 is up-regulated by the EWS/FLI1 oncoprotein and is highly expressed in Ewing tumors. Int J Cancer. 2006;118:1381ā1389.
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PatiƱo-Garcia, A., Zalacain-Diez, M., Lecanda, F. (2009). Molecular Biology of Pediatric Bone Sarcomas. In: San-Julian, M., CaƱadell, J. (eds) Pediatric Bone Sarcomas. Springer, London. https://doi.org/10.1007/978-1-84882-130-9_2
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