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Transcription profiling of very low risk Wilms Tumors show distinctive gene expression, histologic, and clinical features


ABSTRACT: The goal of this study is to define biologically distinct subsets of Very Low Risk Wilms Tumors (VLRWT) using oligonucleotide arrays. Description: 52 tumors from the original case:cohort of 600 tumors from NWTS-5 met the criteria for VLRWT. Thirteen tumors were excluded for quality control reasons, resulting in 39 tumors for analysis. Global gene expression analysis was performed on these 39 tumors. A total of 4,000 probesets representing the greatest variability according to coefficient of variation was utilized for hierarchical clustering, and three clusters were identified. Two subsets within VLRWT are identified that have pathogenetic and molecular differences and apparent differences in risk for relapse. If these predictors can be prospectively validated, this would enable future clinical stratification and broadening the definition of VLRWT. Experiment Overall Design: Global gene expression analysis was performed on 39 tumors that met the criteria of VLRWT and passed quality control parameters in order to define biologically distinct subsets. Experiment Overall Design: Hierarchical clustering identified three tumor clusters (C1, C2 and C3). The top differentially expressed genes were identified by first filtering out probesets with a maximum expression of less than 6.5 in all 39 tumors. Using the remaining 14,452 probesets, the expression of each cluster was compared with the expression in the remaining tumors, and those genes with a p-value <0.00001 and positive or negative fold-change (FC) of greater than 2.5 were identified. This resulted in 161 probesets from the comparison of C1 with C2+C3, 43 probesets from the comparison of C2 with C1+C3, and 71 probesets from the comparison of C3 with C1+C2. The false discovery rates were 0.02%, 0.06% and 0.05% for C1, C2, and C3, respectively. These three lists were combined, resulting in 239 probesets (161 genes) which are provided in Supplemental Table 1, linked below.

ORGANISM(S): Homo sapiens

SUBMITTER: Elizabeth Perlman 

PROVIDER: E-GEOD-14767 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Subsets of very low risk Wilms tumor show distinctive gene expression, histologic, and clinical features.

Sredni Simone T ST   Gadd Samantha S   Huang Chiang-Ching CC   Breslow Norman N   Grundy Paul P   Green Daniel M DM   Dome Jeffrey S JS   Shamberger Robert C RC   Beckwith J Bruce JB   Perlman Elizabeth J EJ  

Clinical cancer research : an official journal of the American Association for Cancer Research 20091110 22


<h4>Purpose</h4>Recent studies suggest that children <24 months with stage I favorable histology Wilms tumors <550 g [very low risk Wilms tumors (VLRWT)] have an excellent prognosis when treated with nephrectomy only, without adjuvant chemotherapy. The identification of risk categories within VLRWT may enable refinement of their definition and optimization of their therapy.<h4>Experimental design</h4>To define biologically distinct subsets, global gene expression analysis was done on 39 VLRWT th  ...[more]

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