Integrated Genomic and Gene Expression Profiling Identifies Two Major Genomic Circuits in Urothelial Carcinoma

摘要: Similar to other malignancies, urothelial carcinoma (UC) is characterized by specific recurrent chromosomal aberrations and gene mutations. However, the interconnection between genomic alterations, how patterns of alterations adhere different molecular subgroups UC, less clear. We applied tiling resolution array CGH 146 cases UC identified a number regions harboring focal amplifications deletions. Several potential oncogenes were included in amplified regions, including known like E2F3, CCND1, CCNE1, as well new candidate genes, such SETDB1 (1q21), BCL2L1 (20q11). next combined genome profiling with global expression, mutation, protein expression data two major circuits operating carcinoma. The first circuit was FGFR3 overexpression 9q CDKN2A second defined E3F3 RB1 deletions, gains 5p, deletions at PTEN 2q36, 16q, 20q, elevated levels. TP53/MDM2 common for advanced tumors within circuits. Our also suggest possible RAS/RAF circuit. worst prognosis showed profile that indicated keratinized phenotype. Taken together, our integrative approach revealed least separate networks linked diversity seen these may reflect distinct pathways tumor development.