Fig. 2: Clonal relationship between gCISs in primary and lung lesions and their interactions in each compartment.

a Schematic structure of the cMET gene and relative location of gene-centered Common Integration Sites (gCIS) in primary tumors and lung metastasis. > denotes SB integration in the 5′ to 3′ direction of the gene and <denotes reverse direction. b Nucleotide-resolution integration site analysis of SB transposons in primary and lung lesions from the same mice in 4 different animals in the cMET gene. For example, mouse 31 (pair #1) has an identical integration site in a primary tumor and in 9 different lung metastases. Pairs #2–4 have a single lung metastasis each with identical integration site as in the primary tumors. c Summary of clonal relationship observed between primary lesions and metastases in 6 different gCISs (details in Supplementary Data 5). d A schematic representation of clonal relationship between primary and lung lesions. For gCIS analysis, tumor biopsies and whole macro-metastasis were subject to ligation-mediated PCR and next-generation DNA sequencing. If a tumor biopsy (a) contains a disseminating clone that gives rise to a large metastasis – and deep sequencing detects the same integration sites in both compartments, clonal relationship can be established. On the other hand, if a tumor biopsy (b) with disseminating metastatic clone is not analyzed for gCIS, or (c) does not spawn a disseminating clone, clonality cannot be demonstrated. e String analysis for interaction among gCISs in primary- and metastasis-specific gCIS. Demarcated are cMET hubs found in both compartments (black circles), as well as Rho signaling/cell migration (blue), protein ubiquitination (orange) and pre-mRNA processing (green) hubs identified in metastasis-only gCISs.