Fig. 4

Molecular evolution of Grade 3 MOC and metastatic disease. a Serum markers of rapid autopsy case. Dashed line indicates maximum normal level. b Schematic of location of metastatic tissues taken at autopsy and haematoxylin and eosin stained sections of metastatic sites (M1 and M3) as well as two areas of the primary tumor, the majority borderline morphology (MBT) and the small area of high-grade invasive tumor identified in the frozen section (G3). Scale bars are 200 µm. c Mutation signatures (S1 - S3) identified by de novo analysis of 5 Grade 3 cases (A-E) showing the shift in mutation signature profile from primary (MBT-E, G3-E) to metastatic sites at autopsy (M1 - M4). d Copy number of primary and metastatic sites showing dramatic increase in structural and copy number alterations in the metastatic sites. Blue, gain; red, loss. e Circos plots illustrating structural variants in primary (MBT-E, G3-E) and metastatic sites (M1–M4) in the rapid autopsy case, and in four independent Grade 3 MOC cases (G3-A, G3-B, G3-C, G3-D). G3-A and G3-B have chromosome 9p amplicons