Early acquisition of homozygous deletions of p16/p19 during squamous cell carcinogenesis and genetic mosaicism in bladder cancer

Abstract

We looked for p16/p19 deletion and p16 promoter methylation, as well as loss of 9p21 heterozygosity in pure squamous cell carcinomas (SCC), and in transitional cell carcinomas (TCC) of the bladder with SCC components. Homozygous deletion of p16/p19 was detected in 11 of 21 (52%) cases of pure SCCs and in three of ten (30%) cases of TCC with SCC. Three cases of TCC with SCC had p16/p19 deletion, hypermethylation of the p16 promoter, or LOH on 9p21 only in the SCC components, suggesting that these molecular alterations occurred preferentially in SCC. Interestingly, homozygous deletion of p16/p19 was observed in squamous metaplasia from bladder cancer patients (®ve of 11, 45%), showing that this change occurred in preneoplastic cells. On the other hand, p16/p19 deletions were not found in squamous metaplasias from non cancerous patients. Hypermethylation of the p16 promoter was observed in two of 14 tumors (14%) and none of seven metaplasias examined. These data suggest that: (a) p16/p19 deletion is associated with early carcinogenesis of SCC of the bladder, and squamous metaplasia of the bladder cancer patient has already sustained genetic changes found in cancer, and (b) genetic mosaicism occurs in cases of TCC with SCC, with the SCC component showing more frequent 9p21 alterations than the TCC component.

Bladder Cancer and Schistosomiasis: Is There a Difference for the Association?

“…This ensures greater accuracy in comparing two groups of tumors (e.g., SA-BC and NSA-BC). Muscheck et al (2000) demonstrated deletion similarities in Schistosoma-associated transitional cell carcinoma (SA-TCC) and Schistosoma-associated squamous cell carcinoma (SA-SCC), compared to what has been previously reported by Kallioniemi et al (1992) on NSA-TCC and Tsutsumi et al (1998) on NSA-SCC. The previous investigators (Kallioniemi et al,1992,Tsutsumi et al,1998, Muscheck et al, 2000, Fadl-Elmula et al, 2002& Albertson and Pinkel, 2003 used the technique of CGH on individual tumor tissues, not pooled tissues of similar pathologies.…”

Inactivation patterns of p16/INK4A in oral squamous cell carcinomas

“…In many types of malignant tumors, homozygous deletion of p16/INK4A gene and hypermethylation of the promoter CpG island are main causes of tumorigenesis (Mead et al, 1994;Brenner et al, 1996;Marchini et al, 1997;Drexler, 1998;Tsutsumi et al, 1998;Wei et al, 1999). In primary tumors, the rate of p16/INK4A point mutation approximates 10% or so (Sartor et al, 1999;Wu et al, 1999).…”

Topographical distribution of allelic loss in individual lung adenocarcinomas with lymph node metastases

“…To evaluate LOH, we used 24 polymorphic microsatellite markers located at the following sites in the 10 genes reported to play a major role in human carcinogenesis: [13][14][15][16][17][18][19][20][21][22] FHIT (3p) (D3S1300, D3S1312, and D3S1313), APC (5q) (D5S346 and D5S82), p16 (9p) (D9S171 and D9S162), TSC-1 (9q) (D9S149, D9S150 and DBH), Int-2 (11q) (INT-2), Rb (13q) (D13S270, D13S273, and D13S176), TSC-2 (16p) (D16S291 and D16S292), p53 (17p) (TP53 and D17S520), Smad 4 (18q) (D18S46, D18S363, and D18S474), and Band M (22q) (D22S1140, D22S1170, and D22S1161). The use of more than one microsatellite marker ensured a higher yield of information for each genomic locus.…”