Genetic aberrations of c-myc and CCND1 in the development of invasive bladder cancer

Abstract

Detrusor muscle invasive transitional cell carcinoma is associated with poor prognosis and is responsible for the majority of bladder cancer related deaths. Amplifications of c-myc and CCND1 are associated with detrusor-muscle-invasive transitional cell carcinoma, however, their precise role in driving disease progression is unclear. Fluorescence in situ hybridisation on archival tissue from 16 patients with primary diagnosis of 5pT2 transitional cell carcinoma and 15 cases with primary pTa/pT1 disease subsequently progressing to detrusor-muscle-invasion was performed, in the latter group both pre and post muscle invasive events were studied. No patients presenting with 5pT2 had amplification of c-myc, two out of 16 (12.5%) had CCND1 amplification. Of patients who developed 5pT2, two out of 15 (13.3%) had amplification of c-myc, both in 5pT2, five out of 15 (33.3%) had CCND1 amplification, two in pTa/pT1 tumours, three in 5pT2 transitional cell carcinomas. In total, two out of 31 (6.5%) of patients' 5pT2 TCCs were amplified for c-myc and six out of 31 (19%) were amplified for CCND1. Eighty-seven per cent (40 out of 46) of tumours were polysomic for chromosome 8 and 80% (37 out of 46) were polysomic for chromosome 11 and this reflected the high copy numbers of c-myc and CCND1 observed. In almost all cases an increase in c-myc/CCND1 copy number occurred prior to invasion and persisted in advanced disease. Amplification of CCND1 or alterations in c-myc/CCND1 early in bladder cancer may have clinical relevance in promoting and predicting progression to detrusor-muscle-invasive transitional cell carcinoma.

HER2/neu overexpression in the development of muscle-invasive transitional cell carcinoma of the bladder

“…Gene amplification rates were low, being present in 8% of both tumour groups, a value similar to previously published rates of 7 and 9% (Sauter et al, 1993;Underwood et al, 1995). The results are also similar to those recently published by our group where polysomy c-myc and CCND1 rates were higher than gene amplification rates (Watters et al, 2002). Polysomy has been shown to occur independently of tumour polyploidy and is not only chromosome specific but also closely related to tumour progression (Watters et al, 2002).…”

MicroRNA-383 inhibits anchorage-independent growth and induces cell cycle arrest of glioma cells by targeting CCND1

“…It can promote G0/G1 to S phase transition, accelerate cell cycle, and consequently promote cell growth. Abnormal expression of CCND1 has been reported in a variety of human tumors, including breast cancer [18,19], bladder cancer [20,21], colon cancer [22,23], and glioma also included [24,25]. Growing evidence demonstrated that CCND1 is a potential therapeutic target in cancer [26,27].…”

Coexistence of Copy Number Changes of Different Genes (INK4A, <i>erbB</i>-1,<i> erbB</i>-2, CMYC, CCND1 and ZNF217) in Urothelial Tumors

“…No specifi c combination of aberrations was found to be signifi cantly more frequent. A number of studies have reported associations between certain oncogene amplifi cation/gain and tumor stage and grade [16,17,[19][20][21][22]26] . The results from the present study give rise to the question whether there is a specifi c prognostic signifi cance of a single oncogene abnormality or if these abnormalities just refl ect the genome instability, which is higher in advanced tumors and are surrogate factors in the genetic instability.…”

“…It was shown to be signifi cantly associated with late-stage and high-grade tumors [20,21] . A recent study suggested that increased CMYC copy numbers might predict invasive tumor growth [22] .…”