Bladder Cancer: A Simple Model Becomes Complex
Giovanni Battista Di Pierro, Caterina Gulia, Cristiano Cristini, Giorgio Fraietta, Lorenzo Marini, Pietro Grande, Vincenzo Gentile and Roberto Piergentili
Pages 395-415 (21)
Bladder cancer is one of the most frequent malignancies in developed countries and it is also characterized by a
high number of recurrences. Despite this, several authors in the past reported that only two altered molecular pathways
may genetically explain all cases of bladder cancer: one involving the FGFR3 gene, and the other involving the TP53
gene. Mutations in any of these two genes are usually predictive of the malignancy final outcome. This cancer may also
be further classified as low-grade tumors, which is always papillary and in most cases superficial, and high-grade tumors,
not necessarily papillary and often invasive. This simple way of considering this pathology has strongly changed in the
last few years, with the development of genome-wide studies on expression profiling and the discovery of small noncoding
RNA affecting gene expression. An easy search in the OMIM (On-line Mendelian Inheritance in Man) database
using “bladder cancer” as a query reveals that genes in some way connected to this pathology are approximately 150, and
some authors report that altered gene expression (up- or down-regulation) in this disease may involve up to 500 coding
sequences for low-grade tumors and up to 2300 for high-grade tumors. In many clinical cases, mutations inside the coding
sequences of the above mentioned two genes were not found, but their expression changed; this indicates that also epigenetic
modifications may play an important role in its development. Indeed, several reports were published about genomewide
methylation in these neoplastic tissues, and an increasing number of small non-coding RNA are either up- or downregulated
in bladder cancer, indicating that impaired gene expression may also pass through these metabolic pathways.
Taken together, these data reveal that bladder cancer is far to be considered a simple model of malignancy. In the present
review, we summarize recent progress in the genome-wide analysis of bladder cancer, and analyse non-genetic, genetic
and epigenetic factors causing extensive gene mis-regulation in malignant cells.
Bladder carcinoma, urinary tract, NMIBC, MICB, carcinoma in situ, CIS, FGFR3, TP53, epigenetics, small noncoding
RNA, environmental causes of bladder carcinoma, urinary tract, NMIBC, MICB, carcinoma in situ, CIS, FGFR3, TP53, epigenetics, small non-coding RNA
Dipartimento di Biologia e Biotecnologie, Sapienza - Universita di Roma, Italy.