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.