Intratumor Heterogeneity and Branched Evolution Revealed by Multiregion Sequencing

Genetic analysis was applied to different regions of renal-cell cancers. The lesions noted in the tumor were not found in every sample, and regions of the tumor had different gene-expression patterns. This suggests that extrapolation from results of a single biopsy may be problematic. Large-scale sequencing analyses of solid cancers have identified extensive heterogeneity between individual tumors. 1 – 6 Genetic intratumor heterogeneity has also been shown 7 – 15 and can contribute to treatment failure and drug resistance. Intratumor heterogeneity may have important consequences for personalized-medicine approaches that commonly rely on single tumor-biopsy samples to portray tumor mutational landscapes. Studies comparing mutational profiles of primary tumors and associated metastatic lesions 16 , 17 or local recurrences 18 have provided evidence of intratumor heterogeneity at nucleotide resolution. Intratumor heterogeneity within primary tumors and associated metastatic sites has not been systematically characterized by next-generation sequencing. We applied exome sequencing, chromosome aberration analysis, . . .