nach oben

Molecular Diagnosis & Therapy

Erschienen in:

01.11.2008 | Cancer

Diagnostic and Prognostic Sarcoma Signatures

verfasst von: Elai Davicioni, Daniel H. Wai, Dr Michael J. Anderson

Erschienen in: Molecular Diagnosis & Therapy | Ausgabe 6/2008

Einloggen, um Zugang zu erhalten

Abstract

Sarcomas are a diverse group of childhood and adult tumors that arise from mesenchymal tissue. In contrast to epithelial tumors, most of which are defined by a specific organ system, sarcomas can arise virtually anywhere in the body, such that their characteristic histopathology and clinical presentation form the core diagnostic criteria.

Precise identification by differential diagnosis is the first element of a successful treatment, since these tumors show wide variation in response to specific therapies and misdiagnosis can lead to suboptimal therapy. However, due to overlapping histopathologic features among the sarcomas, as well as the multiple subtypes or variants within a single histologic group, pathologists and clinicians are increasingly reliant on molecular diagnostic approaches to aid in the differential diagnosis. Gene expression profiling or microarray analysis is now being used to develop expression signatures that appear to be better than histological features or any single biomarker at discriminating tumor types, identifying clinical variants, and modeling complex tumor behavior.

This review examines the current progress in identifying diagnostic and prognostic expression signatures for four sarcomas: rhabdomyosarcoma, Ewing’s family of tumors, synovial sarcoma, and osteosarcoma. In this context, we discuss the current status and future potential for using expression signatures to improve tumor classification, outcome prediction, and therapeutic response in patients with these sarcomas.

Jemal A, Siegel R, Ward E, et al. Cancer statistics, 2008. CA Cancer J Clin 2008 Mar–Apr; 58(2): 71–96PubMedCrossRef

Ries LAG, Smith MA, Gurney JG, et al. Cancer incidence and survival among children and adolescents: United States SEER Program 1975–1995. Bethesda (MD): National Cancer Institute, SEER Program, 1999. NIH Publication no. 99-4649

Linet MS, Ries LA, Smith MA, et al. Cancer surveillance series: recent trends in childhood cancer incidence and mortality in the United States. J Natl Cancer Inst 1999 Jun 16; 91(12): 1051–8PubMedCrossRef

Meyer WH, Spunt SL. Soft tissue sarcomas of childhood. Cancer Treat Rev 2004 May; 30(3): 269–80PubMedCrossRef

Segal NH, Pavlidis P, Antonescu CR, et al. Classification and subtype prediction of adult soft tissue sarcoma by functional genomics. Am J Pathol 2003 Aug; 163(2): 691–700PubMedCrossRef

Wachtel M, Dettling M, Koscielniak E, et al. Gene expression signatures identify rhabdomyosarcoma subtypes and detect a novel t(2;2)(q35;p23) translocation fusing PAX3 to NCOA1. Cancer Res 2004 Aug 15; 64(16): 5539–45PubMedCrossRef

Khan J, Simon R, Bittner M, et al. Gene expression profiling of alveolar rhabdomyosarcoma with cDNA microarrays. Cancer Res 1998 Nov 15; 58(22): 5009–13PubMed

Pandita A, Zielenska M, Thorner P, et al. Application of comparative genomic hybridization, spectral karyotyping, and microarray analysis in the identification of subtype-specific patterns of genomic changes in rhabdomyosarcoma. Neoplasia 1999 Aug; 1(3): 262–75PubMedCrossRef

Davicioni E, Finckenstein FG, Shahbazian V, et al. Identification of a PAX-FKHR gene expression signature that defines molecular classes and determines the prognosis of alveolar rhabdomyosarcomas. Cancer Res 2006 Jul 15; 66(14): 6936–46PubMedCrossRef

10.

DePitta C, Tombolan L, Albiero G, et al. Gene expression profiling identifies potential relevant genes in alveolar rhabdomyosarcoma pathogenesis and discriminates PAX3-FKHR positive and negative tumors. Int J Cancer 2006 Jun 1; 118(11): 2772–81PubMedCrossRef

11.

Lae M, Ahn EH, Mercado GE, et al. Global gene expression profiling of PAX-FKHR fusion-positive alveolar and PAX-FKHR fusion-negative embryonal rhabdomyosarcomas. J Pathol 2007 Jun; 212(2): 143–51PubMedCrossRef

12.

Romualdi C, DePitta C, Tombolan L, et al. Defining the gene expression signature of rhabdomyosarcoma by meta-analysis. BMC Genomics 2006; 7:287PubMedCrossRef

13.

Hancock JD, Lessnick SL. A transcriptional profiling meta-analysis reveals a core EWS-FLI gene expression signature. Cell Cycle 2008 Jan; 7(2): 250–6PubMedCrossRef

14.

Ohali A, Avigad S, Zaizov R, et al. Prediction of high risk Ewing’s sarcoma by gene expression profiling. Oncogene 2004 Nov 25; 23(55): 8997–9006PubMedCrossRef

15.

Schaefer KL, Eisenacher M, Braun Y, et al. Microarray analysis of Ewing’s sarcoma family of tumours reveals characteristic gene expression signatures associated with metastasis and resistance to chemotherapy. Eur J Cancer 2008 Mar; 44(5): 699–709PubMedCrossRef

16.

Nielsen TO, West RB, Linn SC, et al. Molecular characterisation of soft tissue tumours: a gene expression study. Lancet 2002 Apr 13; 359(9314): 1301–7PubMedCrossRef

17.

Nakayama R, Nemoto T, Takahashi H, et al. Gene expression analysis of soft tissue sarcomas: characterization and reclassification of malignant fibrous histio-cytoma. Mod Pathol 2007 Jul; 20(7): 749–59PubMedCrossRef

18.

Nagayama S, Katagiri T, Tsunoda T, et al. Genome-wide analysis of gene expres-sion in synovial sarcomas using a cDNA microarray. Cancer Res 2002 Oct 15; 62(20): 5859–66PubMed

19.

Lee YF, John M, Edwards S, et al. Molecular classification of synovial sarcomas, leiomyosarcomas and malignant fibrous histiocytomas by gene expression profiling. Br J Cancer 2003 Feb 24; 88(4): 510–5PubMedCrossRef

20.

Allander SV, Illei PB, Chen Y, et al. Expression profiling of synovial sarcoma by cDNA microarrays: association of ERBB2, IGFBP2, and ELF3 with epithelial differentiation. Am J Pathol 2002 Nov; 161(5): 1587–95PubMedCrossRef

21.

Francis P, Namlos HM, Muller C, et al. Diagnostic and prognostic gene expression signatures in 177 soft tissue sarcomas: hypoxia-induced transcription profile signifies metastatic potential. BMC Genomics 2007; 8: 73PubMedCrossRef

22.

Fernebro J, Francis P, Eden P, et al. Gene expression profiles relate to SS18/SSX fusion type in synovial sarcoma. Int J Cancer 2006 Mar 1; 118(5): 1165–72PubMedCrossRef

23.

Wolf M, El-Rifai W, Tarkkanen M, et al. Novel findings in gene expression detected in human osteosarcoma by cDNA microarray. Cancer Genet Cytogenet 2000 Dec; 123(2): 128–32PubMedCrossRef

24.

Leonard P, Sharp T, Henderson S, et al. Gene expression array profile of human osteosarcoma. Br J Cancer 2003 Dec 15; 89(12): 2284–8PubMedCrossRef

25.

Ochi K, Daigo Y, Katagiri T, et al. Prediction of response to neoadjuvant chemotherapy for osteosarcoma by gene-expression profiles. Int J Oncol 2004 Mar; 24(3): 647–55PubMed

26.

Man TK, Chintagumpala M, Visvanathan J, et al. Expression profiles of osteosarcoma that can predict response to chemotherapy. Cancer Res 2005 Sep 15; 65(18): 8142–50PubMedCrossRef

27.

Mintz MB, Sowers R, Brown KM, et al. An expression signature classifies chemotherapy-resistant pediatric osteosarcoma. Cancer Res 2005 Mar 1; 65(5): 1748–54PubMedCrossRef

28.

Sanchez-Carbayo M, Belbin TJ, Scotlandi K, et al. Expression profiling of osteosarcoma cells transfected with MDR1 and NEO genes: regulation of cell adhesion, apoptosis, and tumor suppression-related genes. Lab Invest 2003 Apr; 83(4): 507–17PubMed

29.

Nakano T, Tani M, Ishibashi Y, et al. Biological properties and gene expression associated with metastatic potential of human osteosarcoma. Clin Exp Metastasis 2003; 20(7): 665–74PubMedCrossRef

30.

Khanna C, Khan J, Nguyen P, et al. Metastasis-associated differences in gene expression in a murine model of osteosarcoma. Cancer Res 2001 May 1; 61(9): 3750–9PubMed

31.

Khan J, Wei JS, Ringner M, et al. Classification and diagnostic prediction of cancers using gene expression profiling and artificial neural networks. Nat Med 2001 Jun; 7(6): 673–9PubMedCrossRef

32.

Baer C, Nees M, Breit S, et al. Profiling and functional annotation of mRNA gene expression in pediatric rhabdomyosarcoma and Ewing’s sarcoma. Int J Cancer 2004 Jul 10; 110(5): 687–94PubMedCrossRef

33.

Chen QR, Vansant G, Oades K, et al. Diagnosis of the small round blue cell tumors using multiplex polymerase chain reaction. J Mol Diagn 2007 Feb; 9(1): 80–8PubMedCrossRef

34.

Sotiriou C, Khanna C, Jazaeri AA, et al. Core biopsies can be used to distinguish differences in expression profiling by cDNA microarrays. J Mol Diagn 2002 Feb; 4(1): 30–6PubMedCrossRef

35.

Baird K, Davis S, Antonescu CR, et al. Gene expression profiling of human sarcomas: insights into sarcoma biology. Cancer Res 2005 Oct 15; 65(20): 9226–35PubMedCrossRef

36.

Crist WM, Anderson JR, Meza JL, et al. Intergroup rhabdomyosarcoma study-IV: results for patients with nonmetastatic disease. J Clin Oncol 2001 Jun 15; 19(12): 3091–102PubMed

37.

Breneman JC, Lyden E, Pappo AS, et al. Prognostic factors and clinical outcomes in children and adolescents with metastatic rhabdomyosarcoma: a report from the Intergroup Rhabdomyosarcoma Study IV. J Clin Oncol 2003 Jan 1; 21(1): 78–84PubMedCrossRef

38.

NewtonJr WA, Soule EH, Hamoudi AB, et al. Histopathology of childhood sarcomas, Intergroup Rhabdomyosarcoma Studies I and II: clinicopathologic correlation. J Clin Oncol 1988 Jan; 6(1): 67–75PubMed

39.

Leuschner I, NewtonJr WA, Schmidt D, et al. Spindle cell variants of embryonal rhabdomyosarcoma in the paratesticular region: a report of the Intergroup Rhabdomyosarcoma Study. Am J Surg Pathol 1993 Mar; 17(3): 221–30PubMedCrossRef

40.

Shapiro DN, Sublett JE, Li B, et al. Fusion of PAX3 to a member of the forkhead family of transcription factors in human alveolar rhabdomyosarcoma. Cancer Res 1993 Nov 1; 53(21): 5108–12PubMed

41.

Galili N, Davis RJ, Fredericks WJ, et al. Fusion of a fork head domain gene to PAX3 in the solid tumour alveolar rhabdomyosarcoma. Nat Genet 1993 Nov; 5(3): 230–5PubMedCrossRef

42.

Barr FG, Galili N, Holick J, et al. Rearrangement of the PAX3 paired box gene in the paediatric solid tumour alveolar rhabdomyosarcoma. Nat Genet 1993 Feb; 3(2): 113–7PubMedCrossRef

43.

Davis RJ, D’Cruz CM, Lovell MA, et al. Fusion of PAX7 to FKHR by the variant t(l;13)(p36;ql4) translocation in alveolar rhabdomyosarcoma. Cancer Res 1994 Jun 1; 54(11): 2869–72PubMed

44.

Barr FG, Qualman SJ, Macris MH, et al. Genetic heterogeneity in the alveolar rhabdomyosarcoma subset without typical gene fusions. Cancer Res 2002 Aug 15; 62(16): 4704–10PubMed

45.

Sorensen PH, Lynch JC, Qualman SJ, et al. PAX3-FKHR and PAX7-FKHR gene fusions are prognostic indicators in alveolar rhabdomyosarcoma: a report from the children’s oncology group. J Clin Oncol 2002 Jun 1; 20(11): 2672–9PubMedCrossRef

46.

Parham DM, Qualman SJ, Teot L, et al. Correlation between histology and PAX/ FKHR fusion status in alveolar rhabdomyosarcoma: a report from the Children’s Oncology Group. Am J Surg Pathol 2007 Jun; 31(6): 895–901PubMedCrossRef

47.

Asmar L, Gehan EA, Newton WA, et al. Agreement among and within groups of pathologists in the classification of rhabdomyosarcoma and related childhood sarcomas: report of an international study of four pathology classifications. Cancer 1994 Nov 1; 74(9): 2579–88PubMedCrossRef

48.

Newton Jr WA, Gehan EA, Webber BL, et al. Classification of rhabdomy-osarcomas and related sarcomas. Pathologic aspects and proposal for a new classification: an Intergroup Rhabdomyosarcoma study. Cancer 1995 Sep 15; 76(6): 1073–85PubMedCrossRef

49.

Qualman SJ, Coffin CM, Newton WA, et al. Intergroup rhabdomyosarcoma study: update for pathologists. Pediatr Dev Pathol 1998 Nov–Dec; 1(6): 550–61PubMedCrossRef

50.

Tibshirani R, Hastie T, Narasimhan B, et al. Diagnosis of multiple cancer types by shrunken centroids of gene expression. Proc Natl Acad Sci U S A 2002 May 14; 99(10): 6567–72PubMedCrossRef

51.

Tan Y, Shi L, Tong W, et al. Multi-class tumor classification by discriminant partial least squares using microarray gene expression data and assessment of classification models. Comput Biol Chem 2004 Jul; 28(3): 235–44PubMedCrossRef

52.

Zhou X, Wang X, Dougherty ER. Binarization of microarray data on the basis of a mixture model. Mol Cancer Ther 2003 Jul; 2(7): 679–84PubMed

53.

Bicciato S, Luchini A, Di Bello C. PCA disjoint models for multiclass cancer analysis using gene expression data. Bioinformatics 2003 Mar 22; 19(5): 571–8PubMedCrossRef

54.

Pal NR, Aguan K, Sharma A, et al. Discovering biomarkers from gene expression data for predicting cancer subgroups using neural networks and relational fuzzy clustering. BMC Bioinformatics 2007; 8: 5PubMedCrossRef

55.

Fu LM, Fu-Liu CS. Evaluation of gene importance in microarray data based upon probability of selection. BMC Bioinformatics 2005; 6: 67PubMedCrossRef

56.

Albrecht A, Vinterbo SA, Ohno-Machado L. An Epicurean learning approach to gene-expression data classification. Artif Intell Med 2003 May; 28(1): 75–87PubMedCrossRef

57.

Joshi D, Anderson JR, Paidas C, et al. Age is an independent prognostic factor in rhabdomyosarcoma: a report from the Soft Tissue Sarcoma Committee of the Children’s Oncology Group. Pediatr Blood Cancer 2004 Jan; 42(1): 64–73PubMedCrossRef

58.

Grundy R, Anderson J, Gaze M, et al. Congenital alveolar rhabdomyosarcoma: clinical and molecular distinction from alveolar rhabdomyosarcoma in older children. Cancer 2001 Feb 1; 91(3): 606–12PubMedCrossRef

59.

De Bortoli M, Castellino RC, Skapura DG, et al. Patched haploinsufficient mouse rhabdomyosarcoma overexpress secreted phosphoprotein 1 and matrix metal-loproteinases. Eur J Cancer 2007 May; 43(8): 1308–17CrossRef

60.

Dickens DS, Kozielski R, Khan J, et al. Cyclooxygenase-2 expression in pediatrie sarcomas. Pediatr Dev Pathol 2002 Jul–Aug; 5(4): 356–64PubMedCrossRef

61.

Rees H, Williamson D, Papanastasiou A, et al. The MET receptor tyrosine kinase contributes to invasive tumour growth in rhabdomyosarcomas. Growth Factors 2006 Sep; 24(3): 197–208PubMedCrossRef

62.

Scholl FA, Betts DR, Niggli FK, et al. Molecular features of a human rhabdomyosarcoma cell line with spontaneous metastatic progression. Br J Cancer 2000 Mar; 82(6): 1239–45PubMedCrossRef

63.

Yu Y, Davicioni E, Triche TJ, et al. The homeoprotein sixl transcriptionally activates multiple protumorigenic genes but requires ezrin to promote metastasis. Cancer Res 2006 Feb 15; 66(4): 1982–9PubMedCrossRef

64.

Yu Y, Khan J, Khanna C, et al. Expression profiling identifies the cytoskeletal organizer ezrin and the developmental homeoprotein six-1 as key metastatic regulators. Nat Med 2004 Feb; 10(2): 175–81PubMedCrossRef

65.

Langenau DM, Keefe MD, Storer NY, et al. Effects of RAS on the genesis of embryonal rhabdomyosarcoma. Genes Dev 2007 Jun 1; 21(11): 1382–95PubMedCrossRef

66.

Kappler R, Bauer R, Calzada-Wack J, et al. Profiling the molecular difference between patched- and p53-dependent rhabdomyosarcoma. Oncogene 2004 Nov 18; 23(54): 8785–95PubMedCrossRef

67.

Kappler R, Calzada-Wack J, Schnitzbauer U, et al. Molecular characterization of patched-associated rhabdomyosarcoma. J Pathol 2003 Jul; 200(3): 348–56PubMedCrossRef

68.

Carey KA, Segal D, Klein R, et al. Identification of novel genes expressed during rhabdomyosarcoma differentiation using cDNA microarrays. Pathol Int 2006 May; 56(5): 246–55PubMedCrossRef

69.

Graf Finckenstein F, Shahbazian V, Davicioni E, et al. PAX-FKHR function as pangenes by simultaneously inducing and inhibiting myogenesis. Oncogene 2008 Mar 27; 27(14): 2004–14CrossRef

70.

Zhang L, Wang C. Identification of a new class of PAX3-FKHR target promoters: a role of the Pax3 paired box DNA binding domain. Oncogene 2007 Mar 8; 26(11): 1595–605PubMedCrossRef

71.

Ebauer M, Wachtel M, Niggli FK, et al. Comparative expression profiling identifies an in vivo target gene signature with TFAP2B as a mediator of the survival function of PAX3/FKHR. Oncogene 2007 Nov 8; 26(51): 7267–81PubMedCrossRef

72.

Begum S, Emani N, Cheung A, et al. Cell-type-specific regulation of distinct sets of gene targets by Pax3 and Pax3/FKHR. Oncogene 2005 Mar 10; 24(11): 1860–72PubMedCrossRef

73.

Mercado GE, Xia SJ, Zhang C, et al. Identification of PAX3-FKHR-regulated genes differentially expressed between alveolar and embryonal rhabdomy-osarcoma: focus on MYCN as a biologically relevant target. Genes Chromosomes Cancer 2008 Jun; 47(6): 510–20PubMedCrossRef

74.

Epstein JA, Shapiro DN, Cheng J, et al. Pax3 modulates expression of the c-Met receptor during limb muscle development. Proc Natl Acad Sci U S A 1996 Apr 30; 93(9): 4213–8PubMedCrossRef

75.

Bennicelli JL, Fredericks WJ, Wilson RB, et al. Wild type PAX3 protein and the PAX3-FKHR fusion protein of alveolar rhabdomyosarcoma contain potent, structurally distinct transcriptional activation domains. Oncogene 1995 Jul 6; 11(1): 119–30PubMed

76.

Bennicelli JL, Edwards RH, Barr FG. Mechanism for transcriptional gain of function resulting from chromosomal translocation in alveolar rhabdomyosarcoma. Proc Natl Acad Sci U S A 1996 May 28; 93(11): 5455–9PubMedCrossRef

77.

Sublett JE, Jeon IS, Shapiro DN. The alveolar rhabdomyosarcoma PAX3/FKHR fusion protein is a transcriptional activator. Oncogene 1995 Aug 3; 11(3): 545–52PubMed

78.

Fredericks WJ, Galili N, Mukhopadhyay S, et al. The PAX3-FKHR fusion protein created by the t(2;13) translocation in alveolar rhabdomyosarcomas is a more potent transcriptional activator than PAX3. Mol Cell Biol 1995 Mar; 15(3): 1522–35PubMed

79.

Ren YX, Finckenstein FG, Abdueva DA, et al. Mouse mesenchymal stem cells expressing PAX-FKHR form alveolar rhabdomyosarcomas by cooperating with secondary mutations. Cancer Res 2008 Aug 15; 68(16): 6587–97PubMedCrossRef

80.

Scuoppo C, Riess I, Schmitt-Ney M, et al. The oncogenic transcription factor PAX3-FKHR can convert fibroblasts into contractile myotubes. Exp Cell Res 2007 Jul 1; 313(11): 2308–17PubMedCrossRef

81.

Finckenstein FG, Davicioni E, Osborn KG, et al. Transgenic mice expressing PAX3-FKHR have multiple defects in muscle development, including ectopic skeletal myogenesis in the developing neural tube. Transgenic Res 2006 Oct; 15(5): 595–614PubMedCrossRef

82.

Khan J, Bittner ML, Saal LH, et al. cDNA microarrays detect activation of a myogenic transcription program by the PAX3-FKHR fusion oncogene. Proc Natl Acad Sci U S A 1999 Nov 9; 96(23): 13264–9PubMedCrossRef

83.

Morotti RA, Nicol KK, Parham DM, et al. An immunohistochemical algorithm to facilitate diagnosis and subtyping of rhabdomyosarcoma: the Children’s Oncology Group experience. Am J Surg Pathol 2006 Aug; 30(8): 962–8PubMedCrossRef

84.

Kumar S, Perlman E, Harris CA, et al. Myogenin is a specific marker for rhabdomyosarcoma: an immunohistochemical study in paraffin-embedded tissues. Mod Pathol 2000 Sep; 13(9): 988–93PubMedCrossRef

85.

Dias P, Chen B, Dilday B, et al. Strong immunostaining for myogenin in rhabdomyosarcoma is significantly associated with tumors of the alveolar subclass. Am J Pathol 2000 Feb; 156(2): 399–408PubMedCrossRef

86.

Wachtel M, Runge T, Leuschner I, et al. Subtype and prognostic classification of rhabdomyosarcoma by immunohistochemistry. J Clin Oncol 2006 Feb 10; 24(5): 816–22PubMedCrossRef

87.

Ganti R, Skapek SX, Zhang J, et al. Expression and genomic status of EGFR and ErbB-2 in alveolar and embryonal rhabdomyosarcoma. Mod Pathol 2006 Sep; 19(9): 1213–20PubMedCrossRef

88.

Kelly KM, Womer RB, Sorensen PH, et al. Common and variant gene fusions predict distinct clinical phenotypes in rhabdomyosarcoma. J Clin Oncol 1997 May; 15(5): 1831–6PubMed

89.

Williamson D, Lu YJ, Gordon T, et al. Relationship between MYCN copy number and expression in rhabdomyosarcomas and correlation with adverse prognosis in the alveolar subtype. J Clin Oncol 2005 Feb 1; 23(4): 880–8PubMedCrossRef

90.

Ayan I, Dogan O, Kebudi R, et al. Immunohistochemical detection of p53 protein in rhabdomyosarcoma: association with clinicopathological features and outcome. J Pediatr Hematol Oncol 1997 Jan–Feb; 19(1): 48–53PubMedCrossRef

91.

Diniz G, Aktas S, Ortac R, et al. Alternative prognostic factors in pediatric embryonal rhabdomyosarcoma: Nm23 expression, proliferative activity and angiogenesis. Turk J Pediatr 2004 Jul–Sep; 46(3): 239–44PubMed

92.

Blandford MC, Barr FG, Lynch JC, et al. Rhabdomyosarcomas utilize developmental, myogenic growth factors for disease advantage: a report from the Children’s Oncology Group. Pediatrie Blood Cancer 2006 Mar; 46(3): 329–38CrossRef

93.

Anderson J, Ramsay A, Gould S, et al. PAX3-FKHR induces morphological change and enhances cellular proliferation and invasion in rhabdomyosarcoma. Am J Pathol 2001 Sep; 159(3): 1089–96PubMedCrossRef

94.

Pizzo PA, Poplack DG. Principles and practice of pediatrie oncology. 4th ed. Philadelphia (PA): Lippincott Williams & Wilkins, 2002

95.

Bernstein M, Kovar H, Paulussen M, et al. Ewing’s sarcoma family of tumors: current management. Oncologist 2006 May; 11(5): 503–19PubMedCrossRef

96.

Delattre O, Zucman J, Plougastel B, et al. Gene fusion with an ETS DNA-binding domain caused by chromosome translocation in human tumours. Nature 1992 Sep 10; 359(6391): 162–5PubMedCrossRef

97.

Zucman J, Melot T, Desmaze C, et al. Combinatorial generation of variable fusion proteins in the Ewing family of tumours. EMBO J 1993 Dec; 12(12): 4481–7PubMed

98.

Kaneko Y, Yoshida K, Handa M, et al. Fusion of an ETS-family gene, EIAF, to EWS by t(17;22)(ql2;ql2) chromosome translocation in an undifferentiated sarcoma of infancy. Genes Chromosomes Cancer 1996 Feb; 15(2): 115–21PubMedCrossRef

99.

Jeon IS, Davis JN, Braun BS, et al. A variant Ewing’s sarcoma translocation (7;22) fuses the EWS gene to the ETS gene ETV1. Oncogene 1995 Mar 16; 10(6): 1229–34PubMed

100.

Peter M, Couturier J, Pacquement H, et al. A new member of the ETS family fused to EWS in Ewing tumors. Oncogene 1997 Mar 13; 14(10): 1159–64PubMedCrossRef

101.

Sorensen PH, Lessnick SL, Lopez-Terrada D, et al. A second Ewing’s sarcoma translocation, t(21;22), fuses the EWS gene to another ETS-family transcription factor, ERG. Nat Genet 1994 Feb; 6(2): 146–51PubMedCrossRef

102.

Sandberg AA, Bridge JA. Updates on cytogenetics and molecular genetics of bone and soft tissue tumors: Ewing sarcoma and peripheral primitive neuroectodermal tumors. Cancer Genet Cytogenet 2000 Nov; 123(1): 1–26PubMedCrossRef

103.

Bennicelli JL, Barr FG. Genetics and the biologic basis of sarcomas. Curr Opin Oncol 1999 Jul; 11(4): 267–74PubMedCrossRef

104.

Barr FG, Womer RB. Molecular diagnosis of ewing family tumors: too many fusions? J Mol Diagn 2007 Sep; 9(4): 437–40PubMedCrossRef

105.

Kovar H, Jugovic D, Melot T, et al. Cryptic exons as a source of increased diversity of Ewing tumor-associated EWS-FLI1 chimeric products. Genomics 1999 Sep 15; 60(3): 371–4PubMedCrossRef

106.

Ng TL, O’Sullivan MJ, Pallen CJ, et al. Ewing sarcoma with novel translocation t(2;16) producing an in-frame fusion of FUS and FEV. J Mol Diagn 2007 Sep; 9(4): 459–63PubMedCrossRef

107.

Shing DC, McMullan DJ, Roberts P, et al. FUS/ERG gene fusions in Ewing’s tumors. Cancer Res 2003 Aug 1; 63(15): 4568–76PubMed

108.

Lewis TB, Coffin CM, Bernard PS. Differentiating Ewing’s sarcoma from other round blue cell tumors using a RT-PCR translocation panel on formalin-fixed paraffin-embedded tissues. Mod Pathol 2007 Mar; 20(3): 397–404PubMedCrossRef

109.

Hu-Lieskovan S, Zhang J, Wu L, et al. 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 2005 Jun 1; 65(11): 4633–44PubMedCrossRef

110.

Smith R, Owen LA, Trem DJ, et al. Expression profiling of EWS/FLI identifies NKX2.2 as a critical target gene in Ewing’s sarcoma. Cancer Cell 2006 May; 9(5): 405–16PubMedCrossRef

111.

Staege MS, Hutter C, Neumann I, et al. DNA microarrays reveal relationship of Ewing family tumors to both endothelial and fetal neural crest-derived cells and define novel targets. Cancer Res 2004 Nov 15; 64(22): 8213–21PubMedCrossRef

112.

Bandres E, Malumbres R, Escalada A, et al. Gene expression profile of ewing sarcoma cell lines differing in their EWS-FLI1 fusion type.J Pediatr Hematol Oncol 2005 Oct; 27(10): 537–42PubMedCrossRef

113.

Aryee DN, Sommergruber W, Muehlbacher K, et al. Variability in gene expression patterns of Ewing tumor cell lines differing in EWS-FLI1 fusion type. Lab Invest 2000 Dec; 80(12): 1833–44PubMedCrossRef

114.

Nishimori H, Sasaki Y, Yoshida K, et al. The Id2 gene is a novel target of transcriptional activation by EWS-ETS fusion proteins in Ewing family tumors. Oncogene 2002 Nov 28; 21(54): 8302–9PubMedCrossRef

115.

Braunreiter CL, Hancock JD, Coffin CM, et al. Expression of EWS-ETS fusions in NIH3T3 cells reveals significant differences to Ewing’s sarcoma. Cell Cycle 2006 Dec; 5(23): 2753–9PubMedCrossRef

116.

Im YH, Kim HT, Lee C, et al. 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 Mar 15; 60(6): 1536–40PubMed

117.

Ginsberg JP, deAlava E, Ladanyi M, et al. EWS-FLI1 and EWS-ERG gene fusions are associated with similar clinical phenotypes in Ewing’s sarcoma. J Clin Oncol 1999 Jun; 17(6): 1809–14PubMed

118.

deAlava E, Kawai A, Healey JH, et al. EWS-FLI1 fusion transcript structure is an independent determinant of prognosis in Ewing’s sarcoma. J Clin Oncol 1998 Apr; 16(4): 1248–55PubMed

119.

Lin PP, Brody RI, Hamelin AC, et al. Differential transactivation by alternative EWS-FLI1 fusion proteins correlates with clinical heterogeneity in Ewing’s sarcoma. Cancer Res 1999 Apr 1; 59(7): 1428–32PubMed

120.

Zoubek A, Dockhorn-Dworniczak B, Delattre O, et al. Does expression of different EWS chimeric transcripts define clinically distinct risk groups of Ewing tumor patients? J Clin Oncol 1996 Apr; 14(4): 1245–51PubMed

121.

Avigad S, Cohen IJ, Zilberstein J, et al. The predictive potential of molecular detection in the nonmetastatic Ewing family of tumors. Cancer 2004 Mar 1; 100(5): 1053–8PubMedCrossRef

122.

Terrier P, Llombart-Bosch A, Contesso G. Small round blue cell tumors in bone: prognostic factors correlated to Ewing’s sarcoma and neuroectodermal tumors. Semin Diagn Pathol 1996 Aug; 13(3): 250–7PubMed

123.

Burchill SA. Ewing’s sarcoma: diagnostic, prognostic, and therapeutic implications of molecular abnormalities. J Clin Pathol 2003 Feb; 56(2): 96–102PubMedCrossRef

124.

Ramaswamy S, Ross KN, Lander ES, et al. A molecular signature of metastasis in primary solid tumors.Nat Genet 2003 Jan; 33(1): 49–54PubMedCrossRef

125.

Haldar M, Hancock JD, Coffin CM, et al. A conditional mouse model of synovial sarcoma: insights into a myogenic origin. Cancer Cell 2007 Apr; 11(4): 375–88PubMedCrossRef

126.

Sandberg AA, Bridge JA. Updates on the cytogenetics and molecular genetics of bone and soft tissue tumors: synovial sarcoma. Cancer Genet Cytogenet 2002 Feb; 133(1): 1–23PubMedCrossRef

127.

Sun B, Sun Y, Wang J, et al. The diagnostic value of SYT-SSX detected by reverse transcriptase-polymerase chain reaction (RT-PCR) and fluorescence in situ hybridization (FISH) for synovial sarcoma: a review and prospective study of 255 cases. Cancer Sci 2008 Jul; 99(7): 1355–61PubMedCrossRef

128.

Crew AJ, Clark J, Fisher C, et al. Fusion of SYT to two genes, SSX1 and SSX2, encoding proteins with homology to the Kruppel-associated box in human synovial sarcoma. EMBO J 1995 May 15; 14(10): 2333–40PubMed

129.

Clark J, Rocques PJ, Crew AJ, et al. Identification of novel genes, SYT and SSX, involved in the t(X;18)(pll.2;q11.2) translocation found in human synovial sarcoma. Nat Genet 1994 Aug; 7(4): 502–8PubMedCrossRef

130.

Amary MF, Berisha F, Bernardi Fdel C, et al. Detection of SS18-SSX fusion transcripts in formalin-fixed paraffin-embedded neoplasms: analysis of conventional RT-PCR, qRT-PCR and dual color FISH as diagnostic tools for synovial sarcoma.Mod Pathol 2007 Apr; 20(4): 482–96PubMedCrossRef

131.

Folpe AL, Schmidt RA, Chapman D, et al. Poorly differentiated synovial sarcoma: immunohistochemical distinction from primitive neuroectodermal tumors and high-grade malignant peripheral nerve sheath tumors. Am J Surg Pathol 1998 Jun; 22(6): 673–82PubMedCrossRef

132.

Henderson SR, Guiliano D, Presneau N, et al. A molecular map of mesenchymal tumors. Genome Biol 2005; 6(9): R76PubMedCrossRef

133.

Skubitz KM, Skubitz AP. Characterization of sarcomas by means of gene expression. J Lab Clin Med2004 Aug; 144(2): 78–91PubMedCrossRef

134.

Tschoep K, Kohlmann A, Schlemmer M, et al. Gene expression profiling in sarcomas. Crit Rev Oncol Hematol 2007 Aug; 63(2): 111–24PubMedCrossRef

135.

Nielsen TO, Hsu FD, O’Connell X, et al. Tissue microarray validation of epidermal growth factor receptor and SALL2 in synovial sarcoma with comparison to tumors of similar histology. Am J Pathol 2003 Oct; 163(4): 1449–56PubMedCrossRef

136.

Mendelsohn J, Baselga J. Epidermal growth factor receptor targeting in cancer. Semin Oncol 2006 Aug; 33(4): 369–85PubMedCrossRef

137.

Terry J, Saito T, Subramanian S, et al. TLEl as a diagnostic immunohistochemical marker for synovial sarcoma emerging from gene expression profiling studies. Am J Surg Pathol 2007 Feb; 31(2): 240–6PubMedCrossRef

138.

Bergh P, Meis-Kindblom JM, Gherlinzoni F, et al. Synovial sarcoma: identification of low and high risk groups. Cancer 1999 Jun 15; 85(12): 2596–607PubMedCrossRef

139.

Kawai A, Woodruff J, Healey JH, et al. SYT-SSX gene fusion as a determinant of morphology and prognosis in synovial sarcoma. N Engl J Med 1998 Jan 15; 338(3): 153–60PubMedCrossRef

140.

Inagaki H, Nagasaka T, Otsuka T, et al. Association of SYT-SSX fusion types with proliferative activity and prognosis in synovial sarcoma. Mod Pathol 2000 May; 13(5): 482–8PubMedCrossRef

141.

Nilsson G, Skytting B, Xie Y, et al. The SYT-SSX1 variant of synovial sarcoma is associated with a high rate of tumor cell proliferation and poor clinical outcome. Cancer Res 1999 Jul 1; 59(13): 3180–4PubMed

142.

Panagopoulos I, Mertens F, Isaksson M, et al. Clinical impact of molecular and cytogenetic findings in synovial sarcoma. Genes Chromosomes Cancer 2001 Aug; 31(4): 362–72PubMedCrossRef

143.

Ladanyi M, Antonescu CR, Leung DH, et al. Impact of SYT-SSX fusion type on the clinical behavior of synovial sarcoma: a multi-institutional retrospective study of 243 patients. Cancer Res 2002 Jan 1; 62(1): 135–40PubMed

144.

Guillou L, Benhattar J, Bonichon F, et al. Histologic grade, but not SYT-SSX fusion type, is an important prognostic factor in patients with synovial sarcoma: a multicenter, retrospective analysis. J Clin Oncol 2004 Oct 15; 22(20): 4040–50PubMedCrossRef

145.

Ladanyi M. Correlates of SYT-SSX fusion type in synovial sarcoma: getting more complex but also more interesting? J Clin Oncol 2005 May 20; 23(15): 3638–3639; 3639-40PubMedCrossRef

146.

dosSantos NR, deBruijn DR, van Kessel AG. Molecular mechanisms underlying human synovial sarcoma development. Genes Chromosomes Cancer 2001 Jan; 30(1): 1–14PubMedCrossRef

147.

Yang K, Lui WO, Xie Y, et al. Co-existence of SYT-SSX1 and SYT-SSX2 fusions in synovial sarcomas. Oncogene2002 Jun 13; 21(26): 4181–90PubMedCrossRef

148.

Tang N, Song WX, Luo J, et al. Osteosarcoma development and stem cell differentiation. Clin Orthop Relat Res 2008 Sep; 466(9): 2114–30PubMedCrossRef

149.

Hayden JB, Hoang BH. Osteosarcoma: basic science and clinical implications. Orthop Clin North Am 2006 Jan; 37(1): 1–7PubMedCrossRef

150.

Klein MJ, Siegal GP. Osteosarcoma: anatomic and histologic variants. Am J Clin Pathol 2006 Apr; 125(4): 555–81PubMed

151.

Meyers PA, Heller G, Healey J, et al. Chemotherapy for nonmetastatic osteogenic sarcoma: the Memorial Sloan-Kettering experience.J Clin Oncol 1992 Jan; 10(1): 5–15PubMed

152.

Meyers PA, Heller G, Healey JH, et al. Osteogenic sarcoma with clinically detectable metastasis at initial presentation. J Clin Oncol 1993 Mar; 11(3): 449–53PubMed

153.

Ragland BD, Bell WC, Lopez RR, et al. Cytogenetics and molecular biology of osteosarcoma. Lab Invest 2002 Apr; 82(4): 365–73PubMedCrossRef

154.

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 Aug; 145(1): 1–30PubMedCrossRef

155.

Schofield D, Wai D, Triche T. Expression profiling of bone tumors. In:Ladanyi M, Gerald WL, editors. Expression profiling of human tumors. Totowa (NJ): Humana Press, 2003: 359–91CrossRef

156.

Neale G, Su X, Morton CL, et al. Molecular characterization of the pediatric preclinical testing panel. Clin Cancer Res 2008 Jul 15; 14(14): 4572–83PubMedCrossRef

157.

Walkley CR, Qudsi R, Sankaran VG, et al. Conditional mouse osteosarcoma, dependent on p53 loss and potentiated by loss of Rb, mimics the human disease. Genes Dev 2008 Jun 15; 22(12): 1662–76PubMedCrossRef

158.

Sadikovic B, Yoshimoto M, Al-Romaih K, et al. In vitro analysis of integrated global high-resolution DNA methylation profiling with genomic imbalance and gene expression in osteosarcoma. PLoS ONE 2008; 3(7): e2834PubMedCrossRef

159.

Varelias A, Koblar SA, Cowled PA, et al. Human osteosarcoma expresses specific ephrin profiles: implications for tumorigenicity and prognosis. Cancer2002 Aug 15; 95(4): 862–9PubMedCrossRef

160.

Dhaini HR, Thomas DG, Giordano TJ, et al. Cytochrome P450 CYP3A4/5 expression as a biomarker of outcome in osteosarcoma. J Clin Oncol 2003 Jul 1; 21(13): 2481–5PubMedCrossRef

161.

Hoang BH, Kubo T, Healey JH, et al. Expression of LDL receptor-related protein 5 (LRP5) as a novel marker for disease progression in high-grade osteosarcoma. Int J Cancer 2004 Mar; 109(1): 106–11PubMedCrossRef

162.

Srivastava A, Fuchs B, Zhang K, et al. High WT1 expression is associated with very poor survival of patients with osteogenic sarcoma metastasis. Clin Cancer Res 2006 Jul 15; 12 (14 Pt 1): 4237–43PubMedCrossRef

163.

Perbal B, Zuntini M, Zambelli D, et al. Prognostic Value of CCN3 in osteosarcoma. Clin Cancer Res 2008 Feb 1; 14(3): 701–9PubMedCrossRef

164.

Kim SY, Lee CH, Midura BV, et al. Inhibition of the CXCR4/CXCL12 chemokine pathway reduces the development of murine pulmonary metastases. Clin Exp Metastasis 2008; 25(3): 201–11PubMedCrossRef

165.

Laverdiere C, Hoang BH, Yang R, et al. Messenger RNA expression levels of CXCR4 correlate with metastatic behavior and outcome in patients with osteosarcoma. Clin Cancer Res 2005 Apr 1; 11(7): 2561–7PubMedCrossRef

166.

vonLuettichau I, Segerer S, Wechselberger A, et al. A complex pattern of chemokine receptor expression is seen in osteosarcoma. BMC Cancer 2008 Jan 24; 8(1): 23CrossRef

167.

Onda M, Matsuda S, Higaki S, et al. ErbB-2 expression is correlated with poor prognosis for patients with osteosarcoma. Cancer 1996 Jan 1; 77(1): 71–8PubMedCrossRef

168.

Gorlick R, Huvos AG, Heller G, et al. Expression of HER2/erbB-2 correlates with survival in osteosarcoma. J Clin Oncol 1999 Sep; 17(9): 2781–8PubMed

169.

Morris CD, Gorlick R, Huvos G, et al. Human epidermal growth factor receptor 2 as a prognostic indicator in osteogenic sarcoma. Clin Orthop Relat Res 2001 Jan; 382: 59–65PubMedCrossRef

170.

Akatsuka T, Wada T, Kokai Y, et al. ErbB2 expression is correlated with increased survival of patients with osteosarcoma. Cancer 2002 Mar 1; 94(5): 1397–404PubMedCrossRef

171.

Anninga JK, van de Vijver MJ, Cleton-Jansen AM, et al. Overexpression of the HER-2 oncogene does not play a role in high-grade osteosarcomas. Eur J Cancer 2004 May; 40(7): 963–70PubMedCrossRef

172.

Rakesh Kumar V, Gupta N, et al. Prognostic and predictive value of c-erbB2 overexpression in osteogenic sarcoma.J Cancer Res Ther 2006 Jan–Mar; 2(1): 20–3PubMedCrossRef

173.

Yalcin B, Gedikoglu G, Kutluk T, et al. C-erbB-2 expression and prognostic significance in osteosarcoma. Pediatric Blood Cancer 2008 Aug; 51(2): 222–7PubMedCrossRef

174.

Kaseta MK, Khaldi L, Gomatos IP, et al. Prognostic value of bax, bcl-2, and p53 staining in primary osteosarcoma. J Surg Oncol 2008 Mar 1; 97(3): 259–66PubMedCrossRef

175.

Goeman JJ, Oosting J, Cleton-Jansen AM, et al. Testing association of a pathway with survival using gene expression data. Bioinformatics 2005 May 1; 21(9): 1950–7PubMedCrossRef

176.

Dalla-Torre CA, Yoshimoto M, Lee CH, et al. Effects of THBS3, SPARC and SPP1 expression on biological behavior and survival in patients with osteosarcoma. BMC Cancer 2006; 6: 237PubMedCrossRef

177.

Dalla-Torre CA, deToledo SR, Yoshimoto M, et al. Expression of major vault protein gene in osteosarcoma patients. J Orthop Res 2007 Jul; 25(7): 958–63PubMedCrossRef

178.

Fellenberg J, Dechant MJ, Ewerbeck V, et al. Identification of drug-regulated genes in osteosarcoma cells. Int J Cancer 2003 Jul 10; 105(5): 636–43PubMedCrossRef

179.

Fellenberg J, Bernd L, Delling G, et al. Prognostic significance of drug-regulated genes in high-grade osteosarcoma. Mod Pathol 2007 Oct; 20(10): 1085–94PubMedCrossRef

180.

Chano T, Mori K, Scotlandi K, et al. Differentially expressed genes in multidrug resistant variants of U-2 OS human osteosarcoma cells. Oncol Rep 2004 Jun; 11(6): 1257–63PubMed

181.

Mori K, Berreur M, Blanchard F, et al. Receptor activator of nuclear factor-kappaB ligand (RANKL) directly modulates the gene expression profile of RANK-positive Saos-2 human osteosarcoma cells. Oncol Rep 2007 Dec; 18(6): 1365–71PubMed

182.

Rajkumar T, Yamuna M. Multiple pathways are involved in drug resistance to doxorubicin in an osteosarcoma cell line. Anticancer Drugs 2008 Mar; 19(3): 257–65PubMedCrossRef

183.

Walters DK, Steinmann P, Langsam B, et al. Identification of potential chemoresis-tance genes in osteosarcoma. Anticancer Res 2008 Mar–Apr; 28(2A): 673–9PubMed

184.

Ii S, Ueda Y, Shimazaki M, et al. Identification of novel genes involved in the synergistic antitumor effect of caffeine in osteosarcoma cells using cDNA macroarray. Anticancer Res 2008 Mar–Apr; 28(2A): 645–53PubMed

185.

Gillette JM, Chan DC, Nielsen-Preiss SM. Annexin 2 expression is reduced in human osteosarcoma metastases.J Cell Biochem2004 Jul 1; 92(4): 820–32PubMedCrossRef

186.

Duan X, Jia SF, Zhou Z, et al. Association of alphavbeta3 integrin expression with the metastatic potential and migratory and chemotactic ability of human osteosarcoma cells. Clin Exp Metastasis 2004; 21(8): 747–53PubMedCrossRef

187.

Husmann K, Muff R, Bolander ME, et al. Cathepsins and osteosarcoma: expression analysis identifies cathepsin K as an indicator of metastasis. Mol Carcinog 2008 Jan; 47(1): 66–73PubMedCrossRef

188.

Eppert K, Wunder JS, Aneliunas V, et al. Altered expression and deletion of RMO1 in osteosarcoma. Int J Cancer 2005 May 1; 114(5): 738–46PubMedCrossRef

189.

Koshkina NV, Khanna C, Mendoza A, et al. Fas-negative osteosarcoma tumor cells are selected during metastasis to the lungs: the role of the Fas pathway in the metastatic process of osteosarcoma.Mol Cancer Res 2007 Oct; 5(10): 991–9PubMedCrossRef

190.

Gordon N, Koshkina NV, Jia SF, et al. Corruption of the Fas pathway delays the pulmonary clearance of murine osteosarcoma cells, enhances their metastatic potential, and reduces the effect of aerosol gemcitabine.Clin Cancer Res 2007 Aug 1; 13 (15 Pt 1): 4503–10PubMedCrossRef

191.

Fuchs B, Mahlum E, Haider C, et al. High expression of tumor endothelial marker 7 is associated with metastasis and poor survival of patients with osteogenic sarcoma. Gene 2007 Sep 15; 399(2): 137–43PubMedCrossRef

192.

deNigris F, Rossiello R, Schiano C, et al. Deletion of Yin Yang 1 protein in osteosarcoma cells on cell invasion and CXCR4/angiogenesis and metastasis. Cancer Res 2008 Mar 15; 68(6): 1797–808PubMedCrossRef

193.

Khanna C, Wan X, Bose S, et al. The membrane-cytoskeleton linker ezrin is necessary for osteosarcoma metastasis. Nat Med 2004 Feb; 10(2): 182–6PubMedCrossRef

194.

Wan X, Mendoza A, Khanna C, et al. Rapamycin inhibits ezrin-mediated metastat-ic behavior in a murine model of osteosarcoma. Cancer Res 2005 Mar 15; 65(6): 2406–11PubMedCrossRef

195.

Zucchini C, Bianchini M, Valvassori L, et al. Identification of candidate genes involved in the reversal of malignant phenotype of osteosarcoma cells transfected with the liver/bone/kidney alkaline phosphatase gene. Bone 2004 Apr; 34(4): 672–9PubMedCrossRef

196.

Cantiani L, Manara MC, Zucchini C, et al. Caveolin-1 reduces osteosarcoma metastases by inhibiting c-Src activity and met signaling. Cancer Res 2007 Aug 15; 67(16): 7675–85PubMedCrossRef

197.

Manara MC, Bernard G, Lollini PL, et al. CD99 acts as an oncosuppressor in osteosarcoma. Mol Biol Cell 2006 Apr; 17(4): 1910–21PubMedCrossRef

198.

Zucchini C, Rocchi A, Manara MC, et al. Apoptotic genes as potential markers of metastatic phenotype in human osteosarcoma cell lines.Int J Oncol 2008 Jan; 32(1): 17–31PubMed

199.

Dumur CI, Lyons-Weiler M, Sciulli C, et al. Interlaboratory performance of a microarray-based gene expression test to determine tissue of origin in poorly differentiated and undifferentiated cancers. J Mol Diagn 2008 Jan; 10(1): 67–77PubMedCrossRef

200.

Abdueva D, Wing MR, Schaub B, et al. Experimental comparison and evaluation of the Affymetrix exon and U133Plus2 GeneChip arrays. PLoS ONE 2007; 2(9): e913PubMedCrossRef

Titel: Diagnostic and Prognostic Sarcoma Signatures
verfasst von: Elai Davicioni
Daniel H. Wai
Dr Michael J. Anderson
Publikationsdatum: 01.11.2008
Verlag: Springer International Publishing
Erschienen in: Molecular Diagnosis & Therapy / Ausgabe 6/2008
Print ISSN: 1177-1062
Elektronische ISSN: 1179-2000
DOI: https://doi.org/10.1007/BF03256302

Leitlinien kompakt für die Innere Medizin

Mit medbee Pocketcards sicher entscheiden.

^{Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag}

Kostenlos registrieren

Neu im Fachgebiet Innere Medizin

Notfall-TEP der Hüfte ist auch bei 90-Jährigen machbar

26.04.2024 Hüft-TEP Nachrichten

Ob bei einer Notfalloperation nach Schenkelhalsfraktur eine Hemiarthroplastik oder eine totale Endoprothese (TEP) eingebaut wird, sollte nicht allein vom Alter der Patientinnen und Patienten abhängen. Auch über 90-Jährige können von der TEP profitieren.

Niedriger diastolischer Blutdruck erhöht Risiko für schwere kardiovaskuläre Komplikationen

25.04.2024 Hypotonie Nachrichten

Wenn unter einer medikamentösen Hochdrucktherapie der diastolische Blutdruck in den Keller geht, steigt das Risiko für schwere kardiovaskuläre Ereignisse: Darauf deutet eine Sekundäranalyse der SPRINT-Studie hin.

Bei schweren Reaktionen auf Insektenstiche empfiehlt sich eine spezifische Immuntherapie

25.04.2024 Allergien und Intoleranzreaktionen Nachrichten

Insektenstiche sind bei Erwachsenen die häufigsten Auslöser einer Anaphylaxie. Einen wirksamen Schutz vor schweren anaphylaktischen Reaktionen bietet die allergenspezifische Immuntherapie. Jedoch kommt sie noch viel zu selten zum Einsatz.

Therapiestart mit Blutdrucksenkern erhöht Frakturrisiko

25.04.2024 Hypertonie Nachrichten

Beginnen ältere Männer im Pflegeheim eine Antihypertensiva-Therapie, dann ist die Frakturrate in den folgenden 30 Tagen mehr als verdoppelt. Besonders häufig stürzen Demenzkranke und Männer, die erstmals Blutdrucksenker nehmen. Dafür spricht eine Analyse unter US-Veteranen.

Update Innere Medizin

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.

Newsletter bestellen

Springer Medizin

Abstract

Bitte loggen Sie sich ein, um Zugang zu diesem Inhalt zu erhalten

Weitere Artikel der Ausgabe 6/2008

ELISA Test to Detect CDKN2A (p16INK4a) Expression in Exfoliative Cells

Biomarkers for Malignant Pleural Mesothelioma

Biomarkers in the Clinical Diagnosis and Management of Traumatic Brain Injury

CXCL5 Gene Polymorphism Association with Diabetes Mellitus

Glossary of Genetics/Genomics Terms