Genetic and Molecular Mechanisms in Bladder Cancer Development

Abstract

Bladder cancer is the second most common malignancy of the urinary system and the fourth leading cause of cancer. Development and progression of bladder cancer is a multistage process and involves molecular (cell cycle regulatory proteins, such as CABLES, Ki67, and cyclin D1 gene) and genetic abnormalities (oncogenes such as TP63, FGFR3, EGFR, Ras, PIK3CA, MDM2; tumor suppressor genes, including TP53, RBI, CDKN2A/ARF, PTEN and FHIT), chemical and environmental exposures (aromatic amines, aniline dyes, nitrites, nitrates, acrolein, coal, arsenic, and cigarette smoking) or chronic irritation. In addition, it is shown that the microsatellite instability and multiple epigenetic factors may affect development and progression of bladder cancer. The purpose of this review is to highlight the most important molecular and genetic alterations in both low-grade noninvasive and high grade muscle-invasive tumors and molecular mechanisms that have been studied and reported recently, including a discussion of how these may define distinct genetic pathways of bladder cancer.