Genetic and epigenetic aspects of bladder cancer

Abstract

Transitional cell carcinoma of the urinary bladder has a diverse collection of biologic and functional characteristics. This is reflected in differing clinical courses. The diagnosis of bladder cancer is based on the information provided by cystoscopy, the gold standard in combination with urinary cytology findings. Many tumor markers have been evaluated for detecting and monitoring the disease in serum, bladder washes, and urinary specimens. However, none of these biomarkers reported to date has shown sufficient sensitivity and specificity for the detection of the whole spectrum of bladder cancer diseases in routine clinical practice. The limited value of established prognostic markers requires the analysis of new molecular parameters of interest in predicting the prognosis of bladder cancer patients; in particular, the high-risk patient groups at risk of progression and recurrence. Over the past decade, there has been major progress elucidating of the molecular genetic and epigenetic changes leading to the development of transitional cell carcinoma. This review focuses on the recent advances of genetic and epigenetic aspects in bladder cancer, and emphasizes how molecular biology would be likely to affect the future therapies.

Familial and genetic risk of transitional cell carcinoma of the urinary tract

“…chromosome aberrations, somatic mutations of other oncogenes/tumor suppressor genes, epigenetic alterations) ultimately pave the way for tumor progression and, ultimately, metastasis. [73,74] Cytogenetic and molecular genetic studies have identified large-scale structural and numerical chromosome abnormalities as predictors of bladder tumor recurrence and cancer progression. Loss of 9q is the most commonly seen abnormality in low-and high-grade tumors, suggesting that it may be a primary event in the genesis of TCCUT, but the underlying genetic mechanisms (e.g.…”

“…Although these genetic alterations confer only small-to-modest levels of risk, their high prevalence potentially explains a significant proportion of a given cancer's etiology. Numerous single nucleotide polymorphisms in many genes involved in genetic pathways such as carcinogen metabolism, DNA repair, and cell cycle control have been studied as candidate bladder cancer risk modifiers, but results have been inconsistent and meta-analyses have typically not been performed [2,73,78]. A complete review of these studies is beyond the scope of this manuscript; however the references cited above provide additional detail on this subject.…”

Predictive value of progression-related gene classifier in primary non-muscle invasive bladder cancer

“…With this technology, the RNA expression levels of hundreds or even thousands of genes in a tumor can be surveyed simultaneously. The use of high throughput technologies to assess gene expression patterns in tissues, exfoliated cells in urine, or molecules in serum and in circulating cells for many malignancies, including bladder cancer, has been reported [6,7]. These studies open a door to the possibility of rapidly assessing gene expression patterns in individual tumors to determine tumor classification [8], or to predict clinical outcomes [9,10] and response to chemotherapy [11,12].…”

Polymorphisms inXPD,XPCand the risk of death in patients with urinary bladder neoplasms

“…Urinary bladder neoplasms are associated with diverse biological and functional characteristics as reflected by differences in clinical course/outcomes during disease progression [8]. Such diversity in clinical course as well as outcomes is possibly due to genetic differences that make some individuals more susceptible than others.…”