Molecular genesis of non-muscle-invasive urothelial carcinoma (NMIUC)

Abstract

Urothelial carcinoma (UC) is the most common type of bladder cancer in Western nations. Most patients present with the non-muscle-invasive (NMIUC) form of the disease, while up to a third harbour the invasive form (MIUC). Specifically, the aetiology of NMIUC appears to be multifactorial and very different from that of MIUC. Loss of specific tumour suppressor genes as well as gain-of-function mutations in proteins within defined cellular signalling pathways have been implicated in NMIUC aetiology. The regions of chromosome 9 that harbour CDKN2A, CDKN2B, TSC1, PTCH1 and DBC1 are frequently mutated in NMIUC, resulting in functional loss; in addition, HRAS and FGFR3, which are both proto-oncogenes encoding components of the Ras–MAPK signalling pathway, have been found to harbour activating mutations in a large number of NMIUCs. Interestingly, some of these molecular events are mutually exclusive, suggesting functional equivalence. Since several of these driving changes are amenable to therapeutic targeting, understanding the signalling events in NMIUC may offer novel approaches to manage the recurrence and progression of this disease.

CYP1A1 (Ile462Val), CYP1B1 (Ala119Ser and Val432Leu), GSTM1 (null), and GSTT1 (null) Polymorphisms and Bladder Cancer Risk in a Turkish Population

“…Urothelial tumorigenesis is a complex, multistep and multifactorial event, in which different somatic mutations, toxic carcinogenic chemicals, and inflammatory agents are implied to play a role in its ethiogenesis (Lopez-Beltran et al, 2008;Botelho et al, 2010;Pollard et al, 2010). Cigarette smoking is one of the major environmental risk factors for BC due to the presence of procarcinogens in tobacco.…”

miRNA-100 Inhibits Human Bladder Urothelial Carcinogenesis by Directly Targeting mTOR

“…Tumor grade is also an important prognostic factor for patients with bladder cancer. Low-grade bladder cancer is morphologically well differentiated, whereas high-grade bladder cancer is poorly differentiated and more aggressive (3). The mechanisms of bladder cancer carcinogenesis have not been fully investigated.…”

miR-96 regulates FOXO1-mediated cell apoptosis in bladder cancer

“…Transitional cell carcinoma (TCC), the most common histopathological type of bladder cancer, is one of the most prevalent malignancies and a leading cause of genitourinary system cancer mortality worldwide (1,2). Although a number of therapeutic strategies are available, including intravesical chemotherapy, surgery, radiation therapy and systemic chemotherapy, approximately 75% of patients with non-muscle invasive bladder cancer face a five-year survival rate of between 88-98%.…”