Molecular Genetic Abnormalities in Regulators of Cell Cycle and Apoptosis in High Grade Urothelial Carcinoma of Bladder.
Hikmat A Al-Ahmadie, Gopa V Iyer, Oscar Lin, Anuradha Gopalan, Samson W Fine, Yingbei Chen, Satish K Tickoo, Victor E Reuter, Bernard H Bochner, Dean F Bajorin, Matthew I Milowsky, David B Solit. Memorial Sloan-Kettering Cancer Center, New York, NY
Background: Cell cycle dysregulation and inhibition of apoptosis both drive tumorigenesis in multiple malignancies, including urothelial carcinoma (UC). Copy number alteration (CNA) is a well-known mechanism for dysregulation of these cardinal functions. Deletion of CDKN2A and TP53 and amplification of MDM2 has been observed in UC, but the exact frequency and functional consequence of such alterations is less known. We sought to define the frequency of amplification, deletion and mutations of genes that regulate cell cycle or apoptosis in a panel of 96 cases of high-grade UC (HGUC) of bladder.
Design: DNA was isolated from 96 frozen samples of HGUC (including 10 cases of small cell carcinoma of bladder) and analyzed for CNA through comparative genomic hybridization (CGH) using a 1 million oligonucleotide probe array from Agilent. The targeted genes included TP53, MDM2, CCND1, CCNE1, CDKN2A/B, E2F3 and Rb1. Traditional Sanger sequencing to screen for mutations within select genes (TP53, Rb1, and CDKN2A) was also performed.
Results: Table 1 depicts the frequency of CNA and mutations found within the studied genes.
|CDKN2A/B||Del (13), Amp (1), Mut (2)|
|RB1||Del (5), Mut (1)|
|TP53||Mut (12), Del (9)|