Genetic alterations of chromosomes, p53 and p16 genes in low- and high-grade bladder cancer

Abstract

A majority of patients with bladder cancer present with superficial disease and subsequently, some patients show progression to muscle invasive or metastatic disease. Bladder cancer has a complex genetic process and identification of the genetic alterations which occur during progression may lead to the understanding of the nature of the disease and provide the possibility of early treatment. The aim of the present study was to compare the structural and numerical chromosomal differences and changes in the p16 and p53 genes between low-grade (LG) and high-grade (HG) bladder cancer (BC) using cytogenetic and molecular cytogenetic methods. Between March 2009 and March 2010, cytogenetic analyses were carried out on tumor and blood samples in 34 patients with transitional cell type BC, and on blood samples of 34 healthy patients as a control group. Fluorescence in situ hybridization probes for the p16 and p53 genes were also used to screen the alterations in these genes in 32 patients with BC. The patients were divided into two groups (LG and HG) and the findings were compared. A total of 11 (32.3%) patients exhibited LGBC, 22 (64.7%) exhibited HGBC and one (3%) patient exhibited carcinoma in situ. There were no differences between the LGBC and HGBC groups according to the number of chromosomal aberrations (P=0.714); however, differences between alterations of the p16 and p53 genes were significant (P=0.002 and P=0.039). Almost all structural abnormalities were found to be located to the 1q21, 1q32, 3p21 and 5q31 regions in patients with HG tumors. In conclusion, the p16 and p53 genes were altered more prominently in patients with HG tumors compared with LG tumors. The structural abnormalities in the 1q21, 1q32, 3p21 and 5q31 regions were observed more frequently in patients with HG tumors. These regions may play significant roles in the progression of BC, but further studies are required to find candidate genes for a panel of BC.

Research progress on bladder cancer molecular genetics

“…[67] Studies on urothelial bladder carcinoma cell lines showed that these two signaling pathways had different degrees of changes including p53 mutation, pl4 homozygous deletion, RB gene hypermethylation or pl6 homozygous deletion. [68][69][70] Studies on other 12 invasive urothelial bladder carcinoma tumor tissues showed the same results of two signaling pathway changes. [11,71] Mutated p53 protein could not exert cell cycle regulatory function.…”

Up-regulation of p16 by miR-877-3p inhibits proliferation of bladder cancer

“…Alteration of the p16 and p15 genes which occurs at 9p21 appears to be a common event in bladder cancer and p16 has been proposed to be the major deletion target. The frequent inactivation of p16 has been shown to be associated with the progression of bladder cancer to a more malignant phenotype [30–32]. Meanwhile, transduction of p16 antitumor peptide displayed inhibition of bladder cancer in mouse model, which indicated the restoration of p16 to be a probable treatment of bladder cancer [33].…”

T1 high-grade bladder carcinoma outcome: the role of p16, topoisomerase-II α , survivin, and E-cadherin

“…The gene encoding p16 is mutated or downregulated in several cancer cells. Breast carcinoma progression has been related to overexpression of p16 [14], and this has been reported in head and neck squamous carcinoma [15], in prostate carcinoma [16], and also in aggressive subtypes of bladder carcinoma [17][18][19][20].…”