(A) Heatmap depicting the cancer cell fractions of the somatic SNVs
identified in each component. Each column represents one sample; mutations are
reported in rows. The cancer cell fraction and clonality of the mutations were defined
using ABSOLUTE.21 Note that no somatic
mutations were detected in the sarcoma-like component. (B) The barplots
illustrating the mutational signatures of all somatic SNVs of a given histologic component
according to the 96 substitution classification defined by the substitution classes (i.e.
C>A, C>G, C>T, T>A, T>C and T>G bins), and
the 5′ and 3′ sequence context. The height of colored bars represents the
normalized fraction of mutations attributed to each of the 96 sub-bins. The pie charts
show the mutational signatures present in a given component, the sizes of the pie slices
are proportional to the normalized fraction of the mutation types (i.e. C>A,
C>G, C>T, T>A, T>C and T>G).9
(C) Representative micrographs of BRG1, p53 and PTEN expression in the
endometrioid carcinoma, anaplastic carcinoma component and squamous cell carcinoma
component (10× magnification). Loss of BRG1 protein expression is seen in the
three components (lymphocytes and stromal cells serve as internal positive control); the
p53 protein expression pattern differs between tumor components, consistent with their
distinct private TP53 mutations; PTEN expression is retained in the
endometrioid carcinoma areas, while the anaplastic carcinoma and squamous cell carcinoma
components display marked reduction of PTEN expression. (D) Phylogenetic tree
depicting the clonal evolution of the different histologic components. The length of the
branches is proportional to the number of mutations that distinguish a given clone from
its ancestral clone, and selected somatic mutations that define a given clone are shown.
AC, anaplastic carcinoma component; CCF, cancer cell fraction; OEC, ovarian endometrioid
carcinoma; SCC, squamous cell carcinoma component.