BACKGROUND: Unresectable or metastatic disease represents the greatest obstacle to cure for children with rhabdomyosarcoma. In this study we sought to identify gene expression signatures of advanced stage and progressive disease. PROCEDURE: Using oligonucleotide gene expression analysis for a focused set of 60 genes, we analyzed the myogenic expression profiles of 89 rhabdomyosarcomas from the Intergroup Rhabdomyosarcoma Study-IV. RESULTS: While the expression profile of rhabdomyosarcomas closely paralleled gene expression profiles of normal embryonic myogenic progenitors, growth factors were most closely associated with disease progression. Specifically, we identified platelet-derived growth factor (PDGF) receptors and insulin-like growth factor as strongly correlated with decreased failure-free survival. Real-time reverse transcriptase polymerase chain reaction (RT-PCR) of an independent data set suggested that autocrine growth signaling, if present, is not regulated in a simple manner at the transcriptional level. CONCLUSIONS: Increased transcriptional levels of PDGF receptors and insulin-like growth factor are associated with decreased survival in rhabdomyosarcomas. Dual blockade of these growth-factor-signaling pathways may be a valuable strategy in preclinical therapeutic studies.
BACKGROUND: Unresectable or metastatic disease represents the greatest obstacle to cure for children with rhabdomyosarcoma. In this study we sought to identify gene expression signatures of advanced stage and progressive disease. PROCEDURE: Using oligonucleotide gene expression analysis for a focused set of 60 genes, we analyzed the myogenic expression profiles of 89 rhabdomyosarcomas from the Intergroup Rhabdomyosarcoma Study-IV. RESULTS: While the expression profile of rhabdomyosarcomas closely paralleled gene expression profiles of normal embryonic myogenic progenitors, growth factors were most closely associated with disease progression. Specifically, we identified platelet-derived growth factor (PDGF) receptors and insulin-like growth factor as strongly correlated with decreased failure-free survival. Real-time reverse transcriptase polymerase chain reaction (RT-PCR) of an independent data set suggested that autocrine growth signaling, if present, is not regulated in a simple manner at the transcriptional level. CONCLUSIONS: Increased transcriptional levels of PDGF receptors and insulin-like growth factor are associated with decreased survival in rhabdomyosarcomas. Dual blockade of these growth-factor-signaling pathways may be a valuable strategy in preclinical therapeutic studies.
Authors: Jinu Abraham; Suresh I Prajapati; Koichi Nishijo; Beverly S Schaffer; Eri Taniguchi; Aoife Kilcoyne; Amanda T McCleish; Laura D Nelon; Francis G Giles; Argiris Efstratiadis; Robin D LeGallo; Brent M Nowak; Brian P Rubin; Suman Malempati; Charles Keller Journal: Mol Cancer Ther Date: 2011-03-29 Impact factor: 6.261
Authors: Narie Y Storer; Richard M White; Audrey Uong; Emily Price; G Petur Nielsen; David M Langenau; Leonard I Zon Journal: Development Date: 2013-07 Impact factor: 6.868
Authors: E Taniguchi; K Nishijo; A T McCleish; J E Michalek; M H Grayson; A J Infante; H E Abboud; R D Legallo; S J Qualman; B P Rubin; C Keller Journal: Oncogene Date: 2008-08-04 Impact factor: 9.867