title: Gene expression profiling of favorable histology Wilms tumors and its correlation with clinical features.
abstract: The aims of this study were to understand the underlying molecular mechanisms of favorable histology Wilms tumors (WTs) and to classify them based on their molecular signatures. We studied a total of 15 favorable histology WTs using microarrays containing 19,968 cDNAs. First, we found commonly altered genes in WT. A total of 267 cDNAs were significantly overexpressed at least 3-fold in all of the tumors compared with noncancerous kidney and contained known WT-related genes such as IGF II and WT1. The gene with the highest expression change compared with noncancerous kidney was topoisomerase IIalpha. By hierarchical clustering, there was a clear distinction between high-stage and low-stage tumors. A total of 30 cDNAs were found differentially expressed between the high- and low-stage groups. One of them, Stathmin 1, which is involved in the microtubule system, was highly expressed in high-stage tumors compared with the low-stage tumors. The present chemotherapy regimens for WT consist mainly of topoisomerase II inhibitors (i.e., actinomycin D, doxorubicin, and etoposide) and antimicrotubule agents (i.e., vincristine and paclitaxel). Our data suggest that high expression of topoisomerase IIalpha and microtubule-related genes such as tubulin and stathmin 1 may be related to the high chemosensitivity of WT. In addition, retinol-related genes such as CRABP2 and retinol-binding protein 1 were overexpressed in WT, and CRABP2 was more highly expressed in the poor outcome patients, which suggests that retinoid acid may be a potential drug. In summary, our findings suggest that the integration of gene expression data and clinical parameters could aid in detecting aggressive tumors among favorable histology WT and lead to the discovery of new drugs for WT.
authors.affiliation: Laboratory of Cancer Genetics, Van Andel Research Institute, Grand Rapids, Michigan 49503, USA.
authors.forename: Masayuki
authors.initials: M
authors.lastname: Takahashi
authors.forename: Ximing J
authors.initials: XJ
authors.lastname: Yang
authors.forename: Todd T
authors.initials: TT
authors.lastname: Lavery
authors.forename: Kyle A
authors.initials: KA
authors.lastname: Furge
authors.forename: Bart O
authors.initials: BO
authors.lastname: Williams
authors.forename: Maria
authors.initials: M
authors.lastname: Tretiakova
authors.forename: Anthony
authors.initials: A
authors.lastname: Montag
authors.forename: Nicholas J
authors.initials: NJ
authors.lastname: Vogelzang
authors.forename: Gian G
authors.initials: GG
authors.lastname: Re
authors.forename: A Julian
authors.initials: AJ
authors.lastname: Garvin
authors.forename: Stefan
authors.initials: S
authors.lastname: Söderhäll
authors.forename: Susumu
authors.initials: S
authors.lastname: Kagawa
authors.forename: Debra
authors.initials: D
authors.lastname: Hazel-Martin
authors.forename: Agneta
authors.initials: A
authors.lastname: Nordenskjold
authors.forename: Bin Tean
authors.initials: BT
authors.lastname: Teh
mesh_terms: D000951:Antigens, Neoplasm; D002292:Carcinoma, Renal Cell / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000601:surgery; D002675:Child, Preschool; D016000:Cluster Analysis; D004250:DNA Topoisomerases, Type II / Q000096:biosynthesis / Q000235:genetics; D004268:DNA-Binding Proteins; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007223:Infant; D007335:Insulin-Like Growth Factor II / Q000096:biosynthesis / Q000235:genetics; D007680:Kidney Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology* / Q000601:surgery; D009367:Neoplasm Staging; D020411:Oligonucleotide Array Sequence Analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016896:Treatment Outcome; D025721:WT1 Proteins / Q000096:biosynthesis / Q000235:genetics; D009396:Wilms Tumor / Q000235:genetics* / Q000378:metabolism / Q000473:pathology* / Q000601:surgery
chemical_list: D000951:Antigens, Neoplasm; D004268:DNA-Binding Proteins; D025721:WT1 Proteins; D007335:Insulin-Like Growth Factor II; D004250:DNA Topoisomerases, Type II