Molecular genetics of bladder cancer: Emerging mechanisms of tumor initiation and progression

David J. McConkey, Sangkyou Lee, Woonyoung Choi, Mai Tran, Tadeusz Majewski, Sooyong Lee, Arlene Siefker-Radtke, Colin Dinney, Bogdan Czerniak

Research output: Contribution to journalReview articlepeer-review

Abstract

Urothelial cancer has served as one of the most important sources of information about the mutational events that underlie the development of human solid malignancies. Although "field effects" that affect the entire bladder mucosa appear to initiate disease, tumors develop along 2 distinct biological "tracks" that present vastly different challenges for clinical management. Recent whole genome methodologies have facilitated even more rapid progress in the identification of the molecular mechanisms involved in bladder cancer initiation and progression. Specifically, whole organ mapping combined with high resolution, high throughput SNP analyses have identified a novel class of candidate tumor suppressors ("forerunner genes") that localize near more familiar tumor suppressors but are disrupted at an earlier stage of cancer development. Furthermore, whole genome comparative genomic hybridization (CGH) and mRNA expression profiling have demonstrated that the 2 major subtypes of urothelial cancer (papillary/superficial and non-papillary/muscle-invasive) are truly distinct molecular entities, and in recent work our group has discovered that muscle-invasive tumors express molecular markers characteristic of a developmental process known as "epithelial-to-mesenchymal transition" (EMT). Emerging evidence indicates that urothelial cancers contain subpopulations of tumor-initiating cells ("cancer stem cells") but the phenotypes of these cells in different tumors are heterogeneous, raising questions about whether or not the 2 major subtypes of cancer share a common precursor. This review will provide an overview of these new insights and discuss priorities for future investigation.

Original languageEnglish (US)
Pages (from-to)429-440
Number of pages12
JournalUrologic Oncology: Seminars and Original Investigations
Volume28
Issue number4
DOIs
StatePublished - 2010
Externally publishedYes

Keywords

  • Epithelial-to-mesenchymal transition
  • Gene mutation
  • Methylation
  • Stem cell

ASJC Scopus subject areas

  • Oncology
  • Urology

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