title: Wilms tumor--a renal stem cell malignancy?
abstract: Wilms' tumor (WT; nephroblastoma) is the most common pediatric renal malignancy and rated fourth in overall incidence among childhood cancers. It is viewed as a prototype of differentiation failure in human neoplasia as it recapitulates the histology of the nephrogenic zone of the growing fetal kidney. The cellular origin of WT is unclear. However, recent genomic, genetic and epigenetic studies point to an early renal stem/progenitor cell that undergoes malignant transformation as the source for WT. In this context, classical WT shares genes and pathways activated in progenitors committed to the renal lineage. However, direct proof and characterization of the WT initiating cell have remained elusive. Novel methodologies recently adopted from the cancer stem cell scientific field, including the analysis of sorted single human tumor cells, have been applied to WT. These have enabled the identification of cell sub-populations that show similarities-in terms of molecular marker expression-to human fetal kidney progenitors and are, therefore, likely to be derivatives of the same lineage. Further elucidation of the WT cancer stem cell or the cell of origin in human tumors and in transgenic mouse models that generate murine tumors may not only provide novel therapeutic targets but also shed light on the normal kidney stem cell.
authors.affiliation: Pediatric Stem Cell Research Institute, Edmond & Lili Safra Children's Hospital, Sheba Center for Regenerative Medicine, Chaim Sheba Medical Center, Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel.
authors.forename: Naomi
authors.initials: N
authors.lastname: Pode-Shakked
authors.forename: Benjamin
authors.initials: B
authors.lastname: Dekel
mesh_terms: D000818:Animals; D019070:Cell Lineage; D044127:Epigenesis, Genetic; D020869:Gene Expression Profiling / Q000379:methods; D018507:Gene Expression Regulation, Developmental; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007680:Kidney Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D014411:Neoplastic Stem Cells / Q000378:metabolism / Q000473:pathology*; D020411:Oligonucleotide Array Sequence Analysis; D015398:Signal Transduction; D009396:Wilms Tumor / Q000235:genetics / Q000378:metabolism / Q000473:pathology*