From a biological perspective, it is essential
to distinguish signatures that provide diagnos-
tic insights or that are therapeutically infor-
mative from other signatures, particularly when
they share feature similarities. Notable exam-
ples deliberated earlier include distinguishing
MBD4-compromised SBS96 from other signa-
tures withCpG propensity or correctly differ-
entiating signatures that occur predominantly
at CCN and TCN from UV-related SBS7a.
Additionally, we highlight endogenous sig-
natures indicative of pathway defects that are
Degasperiet al.,Science 376 , eabl9283 (2022) 22 April 2022 11 of 15
cohort
GEL
ICGC
Hartwig
number of rare
signatures
in sample
0
1
2
3
CNS samples GEL ICGC Hartwig
Hartwig 78
ICGC
287
GEL
444
26
415 284 63
AB
H
14
GEL-CNS_common_SBS5 GEL-CNS_common_SBS8
GEL-CNS_common_SBS120
GEL-CNS_common_SBS3 GEL-CNS_common_SBS1 GEL-CNS_rare_SBS11_a
GEL-CNS_rare_SBS113
GEL-CNS_rare_SBS11_b
GEL-CNS_rare_SBS14 GEL-CNS_rare_SBS121
GEL-CNS_rare_SBS4
GEL-CNS_rare_SBS17
GEL-CNS_rare_SBS7a
GEL-CNS_rare_SBS119
GEL-CNS_rare_SBS137
GEL-CNS_rare_SBS2+13 GEL-CNS_common_DBS13+20
GEL-CNS_rare_DBS1
GEL-CNS_rare_DBS14
GEL-CNS_rare_DBS2
CDE F
G
mutations
mutations
Common SBS signatures Rare previously reported Rare previuslyunreported DBS signatures
TSB
RSB
Transcription strand bias
Replication strand bias
RSB TSB
TSB TSB
RSB TSB
TSB
TSB
RSB
TSB
T SBBST T SBBST
T SBBST
SBS5
DBS13+20
SBS120
SBS3
SBS1
rare previously reported
rare previously unreported
unassigned
DBS1
DBS14
DBS2
unassigned
100
102
103
101
104
105
106
100
101
102
103
mutations
357198643660 03701776235415561383158683 01 30 0 30 09 1 33 01 3 02 10 1 10 01 0 23 00 2 00
SBS1 SBS3 SBS5 SBS8
SBS120
SBS2 SBS4 SBS7a SBS11 SBS13 SBS14 SBS17
SBS113 SBS119 SBS121 SBS137
100
102
103
101
104
105
106
mutations
0 14110 20 0 1191 00 2 00 10 0 10 01
SBS18 SBS23 SBS126 SBS6 SBS26 SBS35 SBS97
100
102
103
101
104
105
106
mutations
899208983 60 0 40 03 0 20 13 0 03
DBS13 DBS20 DBS1 DBS2 DBS14 DBS11 DBS19
100
102
103
101
104
105
106
SBS8
Contribution of CNS signatures in the GEL cohort
Exposures of CNS SBS signatures found in GEL
Exposures of CNS SBS signatures found
in ICGC and Hartwig only Exposures of CNS DBS signatures
Fig. 6. Summary of SBS signatures and DBS signatures in CNS tumors from
the GEL dataset.(A) CNS tumors from GEL, ICGC and HMF cohorts. (B)MostCNS
tumors have common signatures only (light blue), and a fraction have one rare signature
(maroon). In the pie charts, numbers <5% are not shown. (C) Common SBS signatures
in CNS GEL tumors. (D) Previously reported rare SBS signatures in CNS GEL tumors.
(E) Previously unreported rare SBS signatures in CNS GEL tumors. (F) DBS signatures in
CNS GEL tumors. (G) Distribution of mutational signatures in all CNS GEL tumors.
For each sample, the total number of mutations is shown in a log scale, whereas
signature exposure proportions are colored linearly. Samples are clustered according
to the exposure proportions using hierarchical clustering with average linkage.
(H) Mutational frequencies of common and rare signatures of CNS GEL cancers.
Numbers at the bottom indicate the numbers of samples with each signature.
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