Figure 1. The treatment history and genomic landscape of a metastatic carcinoma with an extreme outlier response to combination therapy.

(A) Schematic representation of the treatment history of the index responder, a patient with metastatic small cell carcinoma of the ureter (PR, partial response; CR, complete response; NED, no evidence of disease). (B) Computed tomography images of the index patient prior to surgery of the recurrent tumor, prior to combined AZD7762 and irinotecan therapy, and one month after combined treatment (left, middle, and right respectively). (C) Somatic abnormalities in the responder’s genome (from outside to inside) included a heavy burden of copy number alterations; mutations at ~10-Mb resolution; regulatory, synonymous, missense, nonsense, and frameshift insertions and deletions (gray, black, orange, red, and green); and intra- and interchromosomal rearrangements (light and dark blue). (D) The allelic fraction of mutations is shown in genes identified by WGS of the post-etoposide/cisplatin tumor and also covered by the IMPACT assay and re-sequenced in the treatment-naïve primary tumor (blue and gray respectively).