Figure Legends
Figure 1. Clinical presentation in this case. Each mutation
detected by targeted-capture sequencing was classified based on the
detected samples and variant allele frequency, while there were no data
available for clone at first relapse. Estimated cell population at each
sample is shown. Tumor at third and fourth relapse showed therapeutic
resistance.
Figure 2. A; The results of copy number analysis of SNP array
for chromosome 9. Red dots at the top represent the signal from each
probe (raw data), and blue line indicates the moving average of red
dots. Red and green lines at the bottom represent allele-specific copy
number. Allelic loss of chromosome 9q including BRINP1 gene was
observed in R2, R3, R4, LN, and Liver samples.
B; Each mutation detected by TCS was classified into 7 clones according
to its variant allele frequency (VAF). VAFs of mutations and estimated
cell population of each sample are shown.
C; The schematic representation of clonal evolution constructed from
somatic mutations detected by TCS. BCOR -ITD was the only truncal
mutation detected in both primary and relapse samples. Additional
mutations accumulated during disease progression were shown.
CN, copy number; D, initial diagnosis; R2, second relapse; R3, third
relapse; R4, fourth relapse; LN, lymph node; VAF, variant allele
frequency.
Supplementary Figure 1. Computed tomography imaging during the
clinical course of the present case, A; at initial diagnosis, B; at
first relapse, C; at second relapse, D; at third relapse, E, F, G, H,
and I; at fourth relapse. White arrows represent tumor site.
Supplementary Figure 2. A; BCOR -ITD (c.5296_5391dup;
NM_0177455) was detected from all tumor samples except R1. The
reference sequence (top) and the sequence data obtained from primary
sample (bottom) are shown. The parental (red) and duplicated (blue)
segments are indicated.
B; Genomic PCR analysis of BCOR exon 15. The PCR products from
samples in D, R1, R2, R3, R4, LN, and Liver are presented. Targeted PCR
and gel electrophoresis of BCOR exon 15 in samples from D, R2,
R3, LN and Liver showed large product.
C; Schema representing structural variant of BCOR -ITD. Parental
segment in PUFD domain was duplicated (ITD).
M, marker: C, control (peripheral blood); D, initial diagnosis; R2,
second relapse; R3, third relapse; R4, fourth relapse; LN, lymph node;
ANK, ankyrin repeats; PUFD, PCGF ubiquitin-like fold discriminator.
Supplementary Figure 3. Results of SNP array analysis in each
sample. Colorful dots at the top represent signal of each probe (raw
data). Red and green lines at the bottom show allele specific copy
number, respectively.
D, initial diagnosis; R2, second relapse; R3, third relapse; R4, fourth
relapse; LN, lymph node.