Sarcomagenesis.
Sarcomagénesis.
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Los sarcomas representan un número heterogéneo de neoplasias que surgen de la transformación de algunas células mesenquimales primitivas. La evidencia ha aumentado de forma considerable respecto de las células pluripotenciales que dan origen a estos tumores y que parecen ser responsables de la iniciación, el mantenimiento, la diferenciación y la proliferación del osteosarcoma, sarcoma sinovial, rabdomiosarcoma y del sarcoma de Ewing. Se han adoptado diferentes métodos para la identificación de células primitivas en los sarcomas, tales como el uso de marcadores de superficie, la citometría de flujo para el aislamiento de células con elevada actividad de la aldehído deshidrogenasa y la realización de análisis de población celular. Esta revisión resume y analiza datos sobre la tumorigénesis de los sarcomas, evaluando su posible papel en la sensibilidad y resistencia a diferentes intervenciones clásicas (quimio y radioterapia), así como nuevas terapias dirigidas molecularmente.
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Burningham Z, Hashibe M, Spector L, Schiffman JD. The epidemiology of sarcoma. Clin Sarcoma Res. 2012;2(1):14.
Fletcher C, Unni K, Mertens F. Pathology and genetics of tumors of soft tissue and bone. Lyon: International Agency for Research on Cancer Press; 2002.
Siegel R, DeSantis C, Virgo K, Stein K, Mariotto A, Smith T, et al. Cancer treatment and survivorship statistics, 2012. CA Cancer J Clin. 2012;62(4):220-41.
Henderson TO, Rajaraman P, Stovall M, Constine LS, Olive A, Smith SA, et al. Risk factors associated with secondary sarcomas in childhood cancer survivors: a report from the childhood cancer survivor study. Int J Radiat Oncol Biol Phys. 2012;84(1):224-30.
Valery PC, Holly EA, Sleigh AC, Williams G, Kreiger N, Bain C. Hernias and Ewing’s sarcoma family of tumours: a pooled analysis and meta-analysis. Lancet Oncol. 2005;6(7):485-90.
Borden EC, Baker LH, Bell RS, Bramwell V, Demetri GD, Eisenberg BL, et al. Soft tissue sarcomas of adults: state of the translational science. Clin Cancer Res. 2003;9(6):1941-56.
Helman LJ, Meltzer P. Mechanisms of sarcoma development. Nat Rev Cancer. 2003;3(9):685-94.
Taylor BS, Barretina J, Maki RG, Antonescu CR, Singer S, Ladanyi M. Advances in sarcoma genomics and new therapeutic targets. Nat Rev Cancer. 2011;11(8):541-57.
Rodriguez R, Rubio R, Menendez P. Modeling sarcomagenesis using multipotent mesenchymal stem cells. Cell Res. 2012;22(1):62-77.
Dominici M, Le Blanc K, Mueller I, Slaper-Cortenbach I, Marini F, Krause D, et al. Minimal criteria for defining multipotent mesenchymal stromal cells. The International Society for Cellular Therapy position statement. Cytotherapy. 2006;8(4):315-7.
Lai RC, Choo A, Lim SK. Derivation and characterization of human ESC-derived mesenchymal stem cells. Methods Mol Biol. 2011;698:141-50.
Crisan M, Yap S, Casteilla L, Chen CW, Corselli M, Park TS, et al. A perivascular origin for mesenchymal stem cells in multiple human organs. Cell Stem Cell. 2008;3(3):301-13.
Mohseny AB, Hogendoorn PC. Concise review: mesenchymal tumors: when stem cells go mad. Stem Cells. 2011;29(3):397-403.
Levings PP, McGarry SV, Currie TP, Nickerson DM, McClellan S, Ghivizzani SC, et al. Expression of an exogenous human Oct-4 promoter identifies tumor-initiating cells in osteosarcoma. Cancer Res. 2009;69(14):5648-55.
Mertens F, Antonescu CR, Hohenberger P, Ladanyi M, Modena P, D’Incalci M, et al. Translocation-related sarcomas. Semin Oncol. 2009;36(4):312-23.
Ohali A, Avigad S, Naumov I, Goshen Y, Ash S, Yaniv I. Different telomere maintenance mechanisms in alveolar and embryonal rhabdomyosarcoma. Genes Chromosomes Cancer. 2008;47(11):965-70.
Ulaner GA, Hoffman AR, Otero J, Huang HY, Zhao Z, Mazumdar M, et al. 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. 2004;41(2):155-62.
Lafferty-Whyte K, Cairney CJ, Will MB, Serakinci N, Daidone MG, Zaffaroni N, et al. A gene expression signature classifying telomerase and ALT immortalization reveals an hTERT regulatory network and suggests a mesenchymal stem cell origin for ALT. Oncogene. 2009;28(43):3765-74.
Hsu JJ, Kamath-Loeb AS, Glick E, Wallden B, Swisshelm K, Rubin BP, et al. Werner syndrome gene variants in human sarcomas. Mol Carcinog. 2010;49(2):166-74.
Meyer S, Kingston H, Taylor AM, Byrd PJ, Last JI, Brennan BM, et al. Rhabdomyosarcoma in Nijmegen breakage syndrome: strong association with perianal primary site. Cancer Genet Cytogenet. 2004;154(2):169-74.
Hicks MJ, Roth JR, Kozinetz CA, Wang LL. Clinicopathologic features of osteosarcoma in patients with Rothmund-Thomson syndrome. J Clin Oncol. 2007;25(4):370-5.
Stephens PJ, Greenman CD, Fu B, Yang F, Bignell GR, Mudie LJ, et al. Massive genomic rearrangement acquired in a single catastrophic event during cancer development. Cell. 2011;144(1):27-40.
Rausch T, Jones DT, Zapatka M, Stütz AM, Zichner T, Weischenfeldt J, et al. Genome sequencing of pediatric medulloblastoma links catastrophic DNA rearrangements with TP53 mutations. Cell. 2012;148(1-2):59-71.
Forment JV, Kaidi A, Jackson SP. Chromothripsis and cancer: causes and consequences of chromosome shattering. Nat Rev Cancer. 2012;12(10):663-70.
Mercado GE, Xia SJ, Zhang C, Ahn EH, Gustafson DM, Laé M, et al. Identification of PAX3-FKHR-regulated genes differentially expressed between alveolar and embryonal rhabdomyosarcoma: focus on MYCN as a biologically relevant target. Genes Chromosomes Cancer. 2008;47(6):510-20.
Ayalon D, Glaser T, Werner H. Transcriptional regulation of IGF-I receptor gene expression by the PAX3-FKHR oncoprotein. Growth Horm IGF Res. 2001;11(5):289-97.
Tsuda M, Davis IJ, Argani P, Shukla N, McGill GG, Nagai M, et al. TFE3 fusions activate MET signaling by transcriptional up-regulation, defining another class of tumors as candidates for therapeutic MET inhibition. Cancer Res. 2007;67(3):919-29.
Guillon N, Tirode F, Boeva V, Zynovyev A, Barillot E, Delattre O. The oncogenic EWS-FLI1 protein binds in vivo GGAA microsatellite sequences with potential transcriptional activation function. PLoS One. 2009;4(3):e4932.
Gangwal K, Sankar S, Hollenhorst PC, Kinsey M, Haroldsen SC, Shah AA, et al. Microsatellites as EWS/FLI response elements in Ewing’s sarcoma. Proc Natl Acad Sci USA. 2008;105(29):10149-54.
Boeva V, Surdez D, Guillon N, Tirode F, Fejes AP, Delattre O, et al. De novo motif identification improves the accuracy of predicting transcription factor binding sites in ChIP-Seq data analysis. Nucleic Acids Res. 2010;38(11):e126.
Kovar H. Downstream EWS/FLI1 - upstream Ewing’s sarcoma. Genome Med. 2010;2(1):8.
Kauer M, Ban J, Kofler R, Walker B, Davis S, Meltzer P, et al. A molecular function map of Ewing’s sarcoma. PLoS One. 2009;4(4):e5415.
Tirode F, Laud-Duval K, Prieur A, Delorme B, Charbord P, Delattre O. Mesenchymal stem cell features of Ewing tumors. Cancer Cell. 2007;11(5):421-9.
Lessnick SL, Dacwag CS, Golub TR. The Ewing’s sarcoma oncoprotein EWS/FLI induces a p53-dependent growth arrest in primary human fibroblasts. Cancer Cell. 2002;1(4):393-401.
Richter GH, Plehm S, Fasan A, Rössler S, Unland R, Bennani-Baiti IM, et al. EZH2 is a mediator of EWS/FLI1 driven tumor growth and metastasis blocking endothelial and neuro-ectodermal differentiation. Proc Natl Acad Sci USA. 2009;106(13):5324-9.
Riggi N, Suvà ML, De Vito C, Provero P, Stehle JC, Baumer K, et al. EWS-FLI-1 modulates miRNA145 and SOX2 expression to initiate mesenchymal stem cell reprogramming toward Ewing sarcoma cancer stem cells. Genes Dev. 2010;24(9):916-32.
Fujino T, Nomura K, Ishikawa Y, Makino H, Umezawa A, Aburatani H, et al. Function of EWS-POU5F1 in sarcomagenesis and tumor cell maintenance. Am J Pathol. 2010;176(4):1973-82.
Yamaguchi S, Yamazaki Y, Ishikawa Y, Kawaguchi N, Mukai H, Nakamura T. EWSR1 is fused to POU5F1 in a bone tumor with translocation t(6;22)(p21;q12). Genes Chromosomes Cancer. 2005;43(2):217-22.
Antonescu CR, Zhang L, Chang NE, Pawel BR, Travis W, Katabi N, et al. 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. 2010;49(12):1114-24.
Möller E, Stenman G, Mandahl N, Hamberg H, Mölne L, van den Oord JJ, et al. 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. 2008;215(1):78-86.
Naka N, Takenaka S, Araki N, Miwa T, Hashimoto N, Yoshioka K, et al. Synovial sarcoma is a stem cell malignancy. Stem Cells. 2010;28(7):1119-31.
Antonescu CR, Yoshida A, Guo T, Chang NE, Zhang L, Agaram NP, et al. KDR activating mutations in human angiosarcomas are sensitive to specific kinase inhibitors. Cancer Res. 2009;69(18):7175-9.
Barretina J, Taylor BS, Banerji S, Ramos AH, Lagos-Quintana M, Decarolis PL, et al. Subtype-specific genomic alterations define new targets for soft-tissue sarcoma therapy. Nat Genet. 2010;42(8):715-21.
Huang HY, Illei PB, Zhao Z, Mazumdar M, Huvos AG, Healey JH, et al. Ewing sarcomas with p53 mutation or p16/p14ARF homozygous deletion: a highly lethal subset associated with poor chemoresponse. J Clin Oncol. 2005;23(3):548-58.
Cho J, Shen H, Yu H, Li H, Cheng T, Lee SB, et al. Ewing sarcoma gene Ews regulates hematopoietic stem cell senescence. Blood. 2011;117(4):1156-66.
Daniels M, Lurkin I, Pauli R, Erbstösser E, Hildebrandt U, Hellwig K, et al. Spectrum of KIT/PDGFRA/BRAF mutations and Phosphatidylinositol-3-Kinase pathway gene alterations in gastrointestinal stromal tumors (GIST). Cancer Lett. 2011;312(1):43-54.
Antonescu CR, Besmer P, Guo T, Arkun K, Hom G, Koryotowski B, et al. Acquired resistance to imatinib in gastrointestinal stromal tumor occurs through secondary gene mutation. Clin Cancer Res. 2005;11(11):4182-90.
Janeway KA, Liegl B, Harlow A, Le C, Perez-Atayde A, Kozakewich H, et al. 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. 2007;67(19):9084-8.
Beroukhim R, Mermel CH, Porter D, Wei G, Raychaudhuri S, Donovan J, et al. The landscape of somatic copy-number alteration across human cancers. Nature. 2010;463(7283):899-905.
Chibon F, Lagarde P, Salas S, Pérot G, Brouste V, Tirode F, et al. 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. 2010;16(7):781-7.
Pedeutour F, Forus A, Coindre JM, Berner JM, Nicolo G, Michiels JF, et al. Structure of the supernumerary ring and giant rod chromosomes in adipose tissue tumors. Genes Chromosomes Cancer. 1999;24(1):30-41.
Sirvent N, Coindre JM, Maire G, Hostein I, Keslair F, Guillou L, et al. 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. 2007;31(10):1476-89.
Singer S, Socci ND, Ambrosini G, Sambol E, Decarolis P, Wu Y, et al. Gene expression profiling of liposarcoma identifies distinct biological types/subtypes and potential therapeutic targets in well-differentiated and dedifferentiated liposarcoma. Cancer Res. 2007;67(14):6626-36.
Mayr C, Hemann MT, Bartel DP. Disrupting the pairing between let-7 and Hmga2 enhances oncogenic transformation. Science. 2007;315(5818):1576-9.
Atiye J, Wolf M, Kaur S, Monni O, Böhling T, Kivioja A, et al. Gene amplifications in osteosarcoma-CGH microarray analysis. Genes Chromosomes Cancer. 2005;42(2):158-63.
Snyder EL, Sandstrom DJ, Law K, Fiore C, Sicinska E, Brito J, et al. c-Jun amplification and overexpression are oncogenic in liposarcoma but not always sufficient to inhibit the adipocytic differentiation programme. J Pathol. 2009;218(3):292-300.
Chibon F, Mariani O, Derré J, Mairal A, Coindre JM, Guillou L, et al. ASK1 (MAP3K5) as a potential therapeutic target in malignant fibrous histiocytomas with 12q14-q15 and 6q23 amplifications. Genes Chromosomes Cancer. 2004;40(1):32-7.
Hélias-Rodzewicz Z, Pérot G, Chibon F, Ferreira C, Lagarde P, Terrier P, et al. YAP1 and VGLL3, encoding two cofactors of TEAD transcription factors, are amplified and overexpressed in a subset of soft tissue sarcomas. Genes Chromosomes Cancer. 2010;49(12):1161-71.
Idbaih A, Coindre JM, Derré J, Mariani O, Terrier P, Ranchère D, et al. Myxoid malignant fibrous histiocytoma and pleomorphic liposarcoma share very similar genomic imbalances. Lab Invest. 2005;85(2):176-81.
Gibault L, Pérot G, Chibon F, Bonnin S, Lagarde P, Terrier P, et al. New insights in sarcoma oncogenesis: a comprehensive analysis of a large series of 160 soft tissue sarcomas with complex genomics. J Pathol. 2011;223(1):64-71.
Adamowicz M, Radlwimmer B, Rieker RJ, Mertens D, Schwarzbach M, Schraml P, et al. Frequent amplifications and abundant expression of TRIO, NKD2, and IRX2 in soft tissue sarcomas. Genes Chromosomes Cancer. 2006;45(9):829-38.
McDermott KM, Zhang J, Holst CR, Kozakiewicz BK, Singla V, Tlsty TD. p16(INK4a) prevents centrosome dysfunction and genomic instability in primary cells. PLoS Biol. 2006;4(3):e51.
Li H, Fan X, Kovi RC, Jo Y, Moquin B, Konz R, et al. Spontaneous expression of embryonic factors and p53 point mutations in aged mesenchymal stem cells: a model of age-related tumorigenesis in mice. Cancer Res. 2007;67(22):10889-98.
Miura M, Miura Y, Padilla-Nash HM, Molinolo AA, Fu B, Patel V, et al. Accumulated chromosomal instability in murine bone marrow mesenchymal stem cells leads to malignant transformation. Stem Cells. 2006;24(4):1095-103.
Mohseny AB, Szuhai K, Romeo S, Buddingh EP, Briaire-de Bruijn I, de Jong D, et al. Osteosarcoma originates from mesenchymal stem cells in consequence of aneuploidization and genomic loss of Cdkn2. J Pathol. 2009;219(3):294-305.
Tolar J, Nauta AJ, Osborn MJ, Panoskaltsis Mortari A, McElmurry RT, Bell S, et al. Sarcoma derived from cultured mesenchymal stem cells. Stem Cells. 2007;25(2):371-9.
Rubio R, Garcia-Castro J, Gutierrez-Aranda I, Paramio J, Santos M, Catalina P, et al. Deficiency in p53 but not retinoblastoma induces the transformation of mesenchymal stem cells in vitro and initiates leiomyosarcoma in vivo. Cancer Res. 2010;70(10):4185-94.
Danielson LS, Menendez S, Attolini CS, Guijarro MV, Bisogna M, Wei J, et al. A differentiation-based microRNA signature identifies leiomyosarcoma as a mesenchymal stem cell-related malignancy. Am J Pathol. 2010;177(2):908-17.
Rodriguez R, Rubio R, Masip M, Catalina P, Nieto A, de la Cueva T, et al. Loss of p53 induces tumorigenesis in p21-deficient mesenchymal stem cells. Neoplasia. 2009;11(4):397-407.
Shimizu T, Ishikawa T, Sugihara E, Kuninaka S, Miyamoto T, Mabuchi Y, et al. c-MYC overexpression with loss of Ink4a/Arf transforms bone marrow stromal cells into osteosarcoma accompanied by loss of adipogenesis. Oncogene. 2010;29(42):5687-99.
Kirsch DG, Dinulescu DM, Miller JB, Grimm J, Santiago PM, Young NP, et al. A spatially and temporally restricted mouse model of soft tissue sarcoma. Nat Med. 2007;13(8):992-7.
Tsumura H, Yoshida T, Saito H, Imanaka-Yoshida K, Suzuki N. Cooperation of oncogenic K-ras and p53 deficiency in pleomorphic rhabdomyosarcoma development in adult mice. Oncogene. 2006;25(59):7673-9.
Hung SC, Yang DM, Chang CF, Lin RJ, Wang JS, Low-Tone Ho L, et al. Immortalization without neoplastic transformation of human mesenchymal stem cells by transduction with HPV16 E6/E7 genes. Int J Cancer. 2004;110(3):313-9.
Rodriguez R, Rubio R, Gutierrez-Aranda I, Melen GJ, Elosua C, García-Castro J, et al. FUS-CHOP fusion protein expression coupled to p53 deficiency induces liposarcoma in mouse but not human adipose-derived mesenchymal stem/stromal cells. Stem Cells. 2011;29(2):179-92.
Funes JM, Quintero M, Henderson S, Martinez D, Qureshi U, Westwood C, et al. Transformation of human mesenchymal stem cells increases their dependency on oxidative phosphorylation for energy production. Proc Natl Acad Sci USA. 2007;104(15):6223-8.
Li N, Yang R, Zhang W, Dorfman H, Rao P, Gorlick R. Genetically transforming human mesenchymal stem cells to sarcomas: changes in cellularphenotype and multilineage differentiation potential. Cancer. 2009;115(20):4795-806.
Wild L, Funes JM, Boshoff C, Flanagan JM. In vitro transformation of mesenchymal stem cells induces gradual genomic hypomethylation. Carcinogenesis. 2010;31(10):1854-62.
Hernando E, Charytonowicz E, Dudas ME, Menendez S, Matushansky I, Mills J, et al. The AKT-mTOR pathway plays a critical role in the development of leiomyosarcomas. Nat Med. 2007;13(6):748-53.
Wu C, Amini-Nik S, Nadesan P, Stanford WL, Alman BA. Aggressive fibromatosis (desmoid tumor) is derived from mesenchymal progenitor cells. Cancer Res. 2010;70(19):7690-8.
Matushansky I, Hernando E, Socci ND, Mills JE, Matos TA, Edgar MA, et al. Derivation of sarcomas from mesenchymal stem cells via inactivation of the Wnt pathway. J Clin Invest. 2007;117(11):3248-57.
Cleton-Jansen AM, Anninga JK, Briaire-de Bruijn IH, Romeo S, Oosting J, Egeler RM, et al. Profiling of high-grade central osteosarcoma and its putative progenitor cells identifies tumourigenic pathways. Br J Cancer. 2009;101(11):1909-18.
