The analysis of clonality presented in this work offers a path forward for clinical sequencing of cancer, and provides means to address recently reported concerns regarding intra-tumor heterogeneity50, 14, 44, 15, 45, 51,52. Analysis using ABSOLUTE can identify alterations present in all cancer cells contributing to the DNA aliquot (Fig. 1), even if such clonal alterations correspond to the minority of observed mutations. Such alterations are candidate founding oncogenic drivers for a given cancer, which may be the preferred therapeutic targets. Further characterization of subclonal somatic alterations in cancer may become important for understanding variable response to targeted therapeutics, with the clonalilty of targeted mutations potentially affecting response level.
