Gene expression profiling of alveolar soft-part sarcoma ASPSReportar como inadecuado




Gene expression profiling of alveolar soft-part sarcoma ASPS - Descarga este documento en PDF. Documentación en PDF para descargar gratis. Disponible también para leer online.

BMC Cancer

, 9:22

First Online: 15 January 2009Received: 15 September 2008Accepted: 15 January 2009DOI: 10.1186-1471-2407-9-22

Cite this article as: Stockwin, L.H., Vistica, D.T., Kenney, S. et al. BMC Cancer 2009 9: 22. doi:10.1186-1471-2407-9-22

Abstract

BackgroundAlveolar soft-part sarcoma ASPS is an extremely rare, highly vascular soft tissue sarcoma affecting predominantly adolescents and young adults. In an attempt to gain insight into the pathobiology of this enigmatic tumor, we performed the first genome-wide gene expression profiling study.

MethodsFor seven patients with confirmed primary or metastatic ASPS, RNA samples were isolated immediately following surgery, reverse transcribed to cDNA and each sample hybridized to duplicate high-density human U133 plus 2.0 microarrays. Array data was then analyzed relative to arrays hybridized to universal RNA to generate an unbiased transcriptome. Subsequent gene ontology analysis was used to identify transcripts with therapeutic or diagnostic potential. A subset of the most interesting genes was then validated using quantitative RT-PCR and immunohistochemistry.

ResultsAnalysis of patient array data versus universal RNA identified elevated expression of transcripts related to angiogenesis ANGPTL2, HIF-1 alpha, MDK, c-MET, VEGF, TIMP-2, cell proliferation PRL, IGFBP1, NTSR2, PCSK1, metastasis ADAM9, ECM1, POSTN and steroid biosynthesis CYP17A1 and STS. A number of muscle-restricted transcripts ITGB1BP3-MIBP, MYF5, MYF6 and TRIM63 were also identified, strengthening the case for a muscle cell progenitor as the origin of disease. Transcript differentials were validated using real-time PCR and subsequent immunohistochemical analysis confirmed protein expression for several of the most interesting changes MDK, c-MET, VEGF, POSTN, CYP17A1, ITGB1BP3-MIBP and TRIM63.

ConclusionResults from this first comprehensive study of ASPS gene expression identifies several targets involved in angiogenesis, metastasis and myogenic differentiation. These efforts represent the first step towards defining the cellular origin, pathogenesis and effective treatment strategies for this atypical malignancy.

Electronic supplementary materialThe online version of this article doi:10.1186-1471-2407-9-22 contains supplementary material, which is available to authorized users.

Download fulltext PDF



Autor: Luke H Stockwin - David T Vistica - Susan Kenney - David S Schrump - Donna O Butcher - Mark Raffeld - Robert H Shoemak

Fuente: https://link.springer.com/



DESCARGAR PDF




Documentos relacionados