title: 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 > or = pT2 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 >/=pT2 had amplification of c-myc, two out of 16 (12.5%) had CCND1 amplification. Of patients who developed > or = pT2, two out of 15 (13.3%) had amplification of c-myc, both in > or = pT2, five out of 15 (33.3%) had CCND1 amplification, two in pTa/pT1 tumours, three in > or = pT2 transitional cell carcinomas. In total, two out of 31 (6.5%) of patients' > or = pT2 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.
authors.affiliation: University Department of Surgery, Level II, Queen Elizabeth Building, Glasgow Royal Infirmary, Glasgow G31 2ER, UK.
authors.forename: A D
authors.initials: AD
authors.lastname: Watters
authors.forename: Z
authors.initials: Z
authors.lastname: Latif
authors.forename: A
authors.initials: A
authors.lastname: Forsyth
authors.forename: I
authors.initials: I
authors.lastname: Dunn
authors.forename: M A
authors.initials: MA
authors.lastname: Underwood
authors.forename: K M
authors.initials: KM
authors.lastname: Grigor
authors.forename: J M S
authors.initials: JM
authors.lastname: Bartlett
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002295:Carcinoma, Transitional Cell / Q000235:genetics* / Q000473:pathology*; D002869:Chromosome Aberrations; D002880:Chromosomes, Human, Pair 11 / Q000235:genetics; D002898:Chromosomes, Human, Pair 8 / Q000235:genetics; D019938:Cyclin D1 / Q000235:genetics*; D004273:DNA, Neoplasm / Q000235:genetics; D018450:Disease Progression; D005260:Female; D005784:Gene Amplification; D016259:Genes, myc / Q000235:genetics*; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness / Q000235:genetics / Q000473:pathology; D009364:Neoplasm Recurrence, Local / Q000235:genetics / Q000473:pathology; D001749:Urinary Bladder Neoplasms / Q000235:genetics* / Q000473:pathology*
chemical_list: D004273:DNA, Neoplasm; D019938:Cyclin D1