Title | WNT/beta-catenin pathway activation in Wilms tumors: a unifying mechanism with multiple entries? |
Publication Type | Journal Article |
Year of Publication | 2009 |
Authors | Corbin M, de Reyniès A, Rickman DS, Berrebi D, Boccon-Gibod L, Cohen-Gogo S, Fabre M, Jaubert F, Faussillon M, Yilmaz F, Sarnacki S, Landman-Parker J, Patte C, Schleiermacher G, Antignac C, Jeanpierre C |
Journal | Genes Chromosomes Cancer |
Volume | 48 |
Issue | 9 |
Pagination | 816-27 |
Date Published | 2009 Sep |
ISSN | 1098-2264 |
Keywords | beta Catenin, Cluster Analysis, DNA Mutational Analysis, Female, Gene Expression Profiling, Humans, Immunohistochemistry, Janus Kinases, Male, Mutation, Nuclear Proteins, Proteomics, Reproducibility of Results, Signal Transduction, STAT3 Transcription Factor, Twist-Related Protein 1, Wilms Tumor, Wnt Proteins, WT1 Proteins |
Abstract | Based on characterization of both genomic and expression status of WT1 and CTNNB1 (beta-catenin) in a series of 60 Wilms tumor samples, combined with genome-wide expression profiling of these tumors, normal mature and fetal kidney controls, we show that WT1/beta-catenin expression was a better classifier than WT1/CTNNB1 mutations. We present molecular data supporting that the WNT pathway is involved in both tumor classes, with and without WT1/beta-catenin alterations. In the tumor class with WT1/beta-catenin alterations, we identified overexpression of 14 previously unreported WNT target genes, including TWIST1. We show that the TWIST1 protein was specifically expressed in these tumors, where staining was restricted to the stromal, nuclear beta-catenin positive, component. By comparing the state of the WNT pathway in tumors without WT1/beta-catenin alterations and fetal kidneys we provide evidence that suggests that these tumors have a heightened level of pathway activation. We characterized mutations of the WNT pathway regulator gene WTX in 16% of this tumor class. Moreover, genome-transcriptome correlation analysis allowed us to identify three other WNT pathway regulator genes that could participate in the activation of the WNT pathway: BCL9 (1p36.2), CTNNBIP1 (1p36.2), and CBY1 (22q13.1). These genes thus represent new potential important actors in WT tumorigenesis. |
DOI | 10.1002/gcc.20686 |
Alternate Journal | Genes Chromosomes Cancer |
PubMed ID | 19530245 |
Related Lab:
Related Faculty:
David Rickman, Ph.D.