Tree models for dependent copy number changes in bladder cancer

We analyzed comparative genomic hybridization data on a collection of 237 bladder cancer tumors with the aim of identifying sets of copy number aberrations (CNAs) that tend to occur together. A test based on Fisher's exact test for pairs, but taking into account multiple testing, showed strong dependencies amongst several pairs of aberrations including (+1q, -11p), (+17q, +20q), (+10p, -17p), (-8p, -17p), (+5p, +10p). To determine whether co-occurrence of CNAs may characterize tumor subtypes, we used two recently proposed methods to construct tree models of tumor progression. We constructed tree models for all the tumors, the tumors of stage pT1, and the tumors of stages pT2-4. The tree models confirmed that most of the non-random events and the associations are the same for different stages. We conclude that the combination of large data sets and tree models provide a useful approach to systematically identifying tumor subgroups characterized by more than a single chromosomal aberration.