Two recent studies in Science try to delineate the variability and evolution of lung tumors.

Andrew Futreal and his colleagues (Science 346, 256–259, 2014) and Charles Swanton his colleagues (Science 346, 251–256, 2014) carried out whole-exome and whole-genome sequencing of multiple regions of 11 and 7 localized lung cancers, respectively, to depict their clonal composition. Both studies found divergent alterations between regions of the same tumor, suggesting branching evolution, but also that a high percentage of driver mutations are shared between regions. Variability seems to be driven by alterations in noncanonical cancer genes.

Futreal and colleagues showed that divergent mutations can be present in multiple regions but that there is intraregion allelic variability. Tumors that relapsed had a higher number of subclonal fractions, suggesting that although single biopsies could be appropriate to evaluate the genetic makeup of a tumor, the level of per-patient heterogeneity should be taken into account to predict progression. Swanton and colleagues corroborate that most driver and regional mutations seem to be clonal, but some regions show subclonal variability, warning about the potential “illusion of clonality” derived from sampling one tumor region.

Both studies suggest that smoking-derived mutational signatures drive early progression, whereas later evolution seems to bear the hallmarks of other mutational processes. Swanton and colleagues propose that events resulting in widespread genomic instability can take place before or after driver mutations appear.

Though the sample size is small, the studies provide a useful picture of the evolution landscape of lung tumors.