For patient #3, three additional regions (R2-4) within the nephrectomy specimen were analyzed....Instead, R3 and R4 shared a loss-of-function TSC1 (Q781*) mutation with concurrent heterozygous loss of chromosome 9, neither of which was present in R1 and R2 (tables 2 and ​and3,3, supplementary figure 9). Thus, distinct genetic events involving tumor suppressors and growth-promoting genes within the same pathway independently occurred in spatially separate areas during the evolution of this tumor....Co-occurrence of these events offers one possible explanation for this patient's favorable response to everolimus monotherapy, despite intratumor heterogeneity.