Science - USA (2022-04-22)

In bladder cancers (three cases), there is a marked
DBS pattern despite low mutational burden
(0.15 to 8 subs/Mb). The cause for this curious
difference in tissue behavior is unclear.

SBS109 is a C>A pattern with tall peaks at

NCA and NCT, although the tallest peaks

are primarily located at ACA and TCT. Only

seven bladder cancers demonstrate this pheno-

type, and it does not have any associated DBS

or TSB. The mutation burden is also low, at

only 0.3 to 3 subs/Mb. SBS107 is seen at low

levels in bladder and kidney cancers (0.04 to

Degasperiet al.,Science 376 , eabl9283 (2022) 22 April 2022 9 of 15

SBS7a

0.000.05

0.10

0.150.20

0.25

C>A C>G C>T T>A T>C T>G

GEL

275

Hartwig 262

ICGC

97

SBS38

0.000.05

0.10

0.150.20

0.25

C>A C>G C>T T>A T>C T>G

GEL

30

Hartwig 62

ICGC

17

SBS129

0.0

0.1

0.2

0.3

0.4

C>A C>G C>T T>A T>C T>G

GEL

2

Hartwig 0

ICGC

0

SBS137

0.00

0.05

0.10

0.15

0.20

C>A C>G C>T T>A T>C T>G

GEL

2

Hartwig 0

ICGC

0

SBS22

0.000.02

0.040.06

0.080.10

0.12

C>A C>G C>T T>A T>C T>G

GEL

3

Hartwig 2

ICGC

45

SBS113

0.000.01

0.020.03

0.040.05

0.060.07

C>A C>G C>T T>A T>C T>G

GEL

3

Hartwig 0

ICGC

0

SBS31

0.000.02

0.040.06

0.080.10

0.120.14

C>A C>G C>T T>A T>C T>G

GEL

48

ICGC

2

SBS35

0.00

0.01

0.02

0.03

0.04

C>A C>G C>T T>A T>C T>G

GEL

0

Hartwig 431

ICGC

301

SBS104

0.00

0.050.10

0.15

0.20

0.25

C>A C>G C>T T>A T>C T>G

GEL

0

Hartwig 2

ICGC

0

SBS111

0.000.01

0.020.03

0.040.05

0.06

C>A C>G C>T T>A T>C T>G

GEL

8

Hartwig 95

ICGC

0

SBS112

0.00

0.02

0.040.06

0.08

0.10

C>A C>G C>T T>A T>C T>G

GEL

4

Hartwig 26

ICGC

0

SBS4

0.000.01

0.020.03

0.040.05

0.06

C>A C>G C>T T>A T>C T>G

GEL

898

Hartwig 346

ICGC

301

SBS94

0.000.02

0.040.06

0.080.10

0.120.14

C>A C>G C>T T>A T>C T>G

GEL

13

Hartwig 3

ICGC

1

SBS107

0.000.01

0.020.03

0.040.05

0.06

C>A C>G C>T T>A T>C T>G

GEL

1461

Hartwig 92

ICGC

403

SBS109

0.000.02

0.040.06

0.080.10

0.12

C>A C>G C>T T>A T>C T>G

GEL

7

Hartwig 66

ICGC

0

Biliary

Bladder

Bone_SoftTissue

Breast

CNS

Colorectal

Esophagus

Head_neck

Kidney

Liver

Lung

Lymphoid

Myeloid

NET

Oral_Oropharyngeal

Ovary

Pancreas

Prostate

Skin

Stomach

Uterus

A

C

D

F

Signatures occurring at CCN and TCN, similar to UV-related SBS7a

Signatures presenting T>A, with similarities to AAI-associated SBS22

Signatures indicating prior platinum exposure

Signatures with strong C>A components,

with similarities to tobacco-associated SBS4

-0.5

0.0

0.5

1.0

Pearson correlation

DBS1SBS7aDBS1SBS38DBS1

SBS129

DBS1

SBS137

GEL

ICGC

Hartwig

8 12211 200 100

-0.5

0.0

0.5

1.0

Pearson correlation

DBS5+18

SBS31

DBS5+18

SBS35

DBS5+18SBS104DBS5+18SBS111DBS5+18SBS112

8 1 11 024 002 1 03 203

-0.5

0.0

0.5

1.0

Pearson correlation

DBS2SBS4 DBS2SBS94DBS2

SBS107

DBS2

SBS109

736 201 2 10 10 1

Correlation of exposures,

UV-like signatures

Correlation of exposures,

platinum-like signatures

Correlation of exposures,

tobacco-like signatures

B

E

G

Hartwig 559

Fig. 5. Signatures associated with environmental mutational processes.
(A) SBS signatures occurring at CCN and TCN, with similarities to UV-related
SBS7a. (B) Correlations of the signatures in (A) with DBS signatures. (C) SBS
signatures presenting T>A, with similarities to AAI-associated SBS22. (D) SBS
signatures indicating prior platinum exposure. (E) Correlations of the
signatures in (D) with DBS signatures. (F) SBS signatures presenting C>A with

similarities to tobacco-associated SBS4. (G) Correlation of the signatures in (F)

with DBS signatures. The number in each column indicates the number of

organs implicated in the correlative analyses. A correlation is computed

independently for each organ, and correlations are displayed as a box plot.

Box plots denote median (horizontal line) and 25th to 75th percentiles (boxes).

The lower and upper whiskers extend 1.5 × IQR.

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