A nonlinear clonal evolution model derived from the observation of mosaic amplification of receptor tyrosine kinases (RTKs) in glioblastoma multiforme (GBM). The primary tumor and all of its derivatives carry the early driver mutation that initiates tumorigenesis. Multiple progression driver mutations can occur in a non-linear manner, creating subpopulations with variable levels of fitness. Many times, a dominant clone emerges before another round of diversification and selection pushes the clonal evolution forward. However, as illustrated by the coexistence of subclones with amplification of different RTKs in some GBMs, subclones may coexist because of either similar fitness levels or a cooperative relationship for enhanced tumor growth potential. Individual subclones and different combinations of them may occupy specific niches within the tumor microenvironment. Relevant genes and niches from the Snuderl et al. study  are indicated in parentheses.