Post on 24-Dec-2015
Supplementary Figure 1. Somatic mutation spectrum#
Subs
tituti
ons
# Substitutions per Mb
b
c
a#
Subs
tituti
ons
per M
b
Repeats
Pseudogenes
Whole genome
Splice sites
Non-coding RNA
Intron
Promoter5’ U
TR3’ U
TRCDS
Supplementary Figure 2. TP53 mutations associated with chromosomal instability and clinical variables
c.CIN ( p = 3.12e-05)
b.
a.
Tumour Grade ( p = 0.0075)
p53 mutation: n=31
p53 wild type: n=51
20 40 60 80 100 1200.
00.
20.
40.
60.
81.
0
DFS
Months
Sur
viva
l Pro
babi
lity
p = 0.136
Nucleotide-binding ATP-binding
ERBB2: L755P,S ERBB2: G776SV777A,L,M
JAK1:L910P JAK1: Q644H,V645F
JAK1: S703I
ACRG-HCC mutationACRG-HCC mutation (recurrent)Known mutationKnown mutation (recurrent)Known mutation (activating)Known mutation (resistant)
Supplementary Figure 3. Alignment of the mutations in kinase domains of JAK1, JAK2, JAK3 and ERBB2
Supplementary Figure 4. JAK inhibitors inhibit JAK1 S703I mutant-mediated activation of p-STAT3 in Ba/F3 cells
BMS-911543
DMSORuxoliti
nib
Stat3
pStat3
Actin
Supplementary Figure 5. Frequencies of copy number gain and loss for chromosomal arms
% T
umou
r Sam
ples
Supplementary Figure 6. Selective amplification and deletion of cancer genes
Oncogene
G-s
core
Am
plifi
catio
n
CNV Regions Non-CNV Regions
Tumor SuppressorOther
G-s
core
Del
etion
a
b Oncogene Tumor SuppressorOther
Oncogene Tumor SuppressorOther Oncogene Tumor SuppressorOther
CNV Regions Non-CNV Regions
Supplementary Figure 7. Overview of cancer pathways impacted by genomic alterations
Down RegulationUp RegulationMutation Amplification Deletion No Change
Supplementary Figure 8. Genomic alterations of key genes and pathways across three subclasses
Pathway alterationMutation
Amplification
Not altered
Alteration Status
Deletion
HBV Integration
S1 S2 S3
Map to reference genome hg19
(SOAP2)
Predict mutant alleles in tumors (SOAPsnv)
Predicted somatic mutation
Performed on tumour and normal separately
Read Depth ≥ 10Read SupportBinomial test
p > 0.01
Quality ScoreWilcoxon rank sum
test p > 0.01
Mutant allele frequency difference
≥ 20%
Mutant allele enriched in
repeatedly aligned reads?
Mutant allele enriched within 10 bps of read ends?
QC sequence readsCollect read support
info on all sites
Tumor vs. Normalmutant allele frequency
Fisher’s Exact testp < 0.01
Y
Y
Y
Y
N
N Y
Supplementary Figure 9. Somatic SNV detection work flow
Sequenom validation497