Tree models for dependent copy number changes in bladder cancer

We analyzed comparative genomic hybridization data on a collection of 237 b ladder cancer tumors with the aim of identifying sets of copy number aberra tions (CNAs) that tend to occur together. A test based on Fisher's exact te st for pairs, but taking into account multiple testing, showed strong depen dencies amongst several pairs of aberrations including (+1q, -11p), (+17q, +20q), (+10p, -17p), (-8p, -17p), (+5p, +10p). To determine whether co-occu rrence of CNAs may characterize tumor subtypes, we used two recently propos ed methods to construct tree models of tumor progression. We constructed tr ee models for all the tumors, the tumors of stage pT1, and the tumors of st ages pT2-4. The tree models confirmed that most of the non-random events an d 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 si ngle chromosomal aberration.