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Table 2 Breast tumours with each COSMIC signature present across tumour subtypes

From: Mutational landscape differences between young-onset and older-onset breast cancer patients

Signature

Age group

Basal-like

HER2+

Luminal A

Luminal B

Normal-like

p-value

Proposed Etiology

Signature 1

Total

107 (73%)

56 (81%)

330 (77%)

139 (76%)

14 (64%)

0.45

Spontaneous deamination of 5-methylcytosine

Young

14 (82%)

2 (67%)

28 (74%)

11 (61%)

1 (100%)

0.65

Older

93 (72%)

54 (82%)

302 (77%)

128 (78%)

13 (62%)

0.27

Oldest

36 (80%)

20 (74%)

175 (80%)

61 (81%)

4 (67%)

0.80

Signature 2

Total

28 (19%)

47 (68%)

169 (39%)

59 (32%)

8 (36%)

< 0.01*

AID/APOBEC

Young

3 (18%)

2 (67%)

14 (37%)

2 (11%)

1 (100%)

0.04*

Older

25 (19%)

45 (68%)

155 (40%)

57 (35%)

7 (33%)

< 0.01*

Oldest

12 (27%)

19 (70%)

82 (37%)

22 (29%)

3 (50%)

< 0.01*

Signature 3

Total

134 (92%)

46 (67%)

252 (59%)

136 (75%)

15 (68%)

< 0.01*

Defective DNA double-strand break repair by homologous recombination

Young

17 (100%)

1 (33%)

20 (53%)

14 (78%)

1 (100%)

< 0.01*

Older

117 (91%)

45 (68%)

232 (59%)

122 (74%)

14 (67%)

< 0.01*

Oldest

41 (91%)

18 (67%)

125 (57%)

55 (73%)

3 (50%)

< 0.01*

Signature 4

Total

26 (18%)

4 (6%)

48 (11%)

24 (13%)

3 (14%)

0.11

Smoking tobacco

Young

3 (18%)

1 (33%)

6 (16%)

5 (28%)

0 (0%)

0.60

Older

23 (18%)

3 (5%)

42 (11%)

19 (12%)

3 (14%)

0.07

Oldest

7 (16%)

2 (7%)

24 (11%)

8 (11%)

1 (17%)

0.75

Signature 5

Total

17 (12%)

18 (26%)

145 (34%)

50 (27%)

3 (14%)

< 0.01*

Unknown

Young

1 (6%)

0 (0%)

13 (34%)

7 (39%)

0 (0%)

0.08

Older

16 (12%)

18 (27%)

132 (34%)

43 (26%)

3 (14%)

< 0.01*

Oldest

4 (9%)

9 (33%)

82 (37%)

19 (25%)

2 (33%)

< 0.01*

Signature 6

Total

23 (16%)

7 (10%)

61 (14%)

25 (14%)

1 (5%)

0.64

Defective DNA mismatch repair

Young

3 (18%)

0 (0%)

8 (21%)

4 (22%)

0 (0%)

1.00

Older

20 (16%)

7 (11%)

53 (14%)

21 (13%)

1 (5%)

0.75

Oldest

4 (9%)

4 (15%)

34 (16%)

10 (13%)

0 (0%)

0.78

Signature 7

Total

15 (10%)

17 (25%)

98 (23%)

30 (16%)

5 (23%)

< 0.01*

UV light

Young

2 (12%)

1 (33%)

6 (16%)

2 (11%)

0 (0%)

0.75

Older

13 (10%)

16 (24%)

92 (24%)

28 (17%)

5 (24%)

< 0.01*

Oldest

4 (9%)

5 (19%)

51 (23%)

8 (11%)

2 (33%)

0.03*

Signature 8

Total

27 (18%)

11 (16%)

86 (20%)

39 (21%)

4 (18%)

0.90

Unknown

Young

5 (29%)

3 (100%)

5 (13%)

5 (28%)

0 (0%)

0.02*

Older

22 (17%)

8 (12%)

81 (21%)

34 (21%)

4 (19%)

0.51

Oldest

6 (13%)

3 (11%)

52 (24%)

17 (23%)

1 (17%)

0.38

Signature 9

Total

24 (16%)

9 (13%)

63 (15%)

34 (19%)

6 (27%)

0.38

Polymerase η

Young

2 (12%)

0 (0%)

6 (16%)

4 (22%)

0 (0%)

0.88

Older

22 (17%)

9 (14%)

57 (15%)

30 (18%)

6 (29%)

0.38

Oldest

9 (20%)

4 (15%)

35 (16%)

16 (21%)

0 (0%)

0.69

Signature 10

Total

5 (3%)

2 (3%)

25 (6%)

11 (6%)

3 (14%)

0.28

Defective polymerase POLE

Young

1 (6%)

0 (0%)

0 (0%)

0 (0%)

0 (0%)

0.27

Older

4 (3%)

2 (3%)

25 (6%)

11 (7%)

3 (14%)

0.20

Oldest

1 (2%)

2 (7%)

12 (5%)

4 (5%)

1 (17%)

0.48

Signature 11

Total

5 (3%)

4 (6%)

33 (8%)

13 (7%)

0 (0%)

0.34

Alkylating agents (e.g. temozolomide)

Young

2 (12%)

0 (0%)

3 (8%)

2 (11%)

0 (0%)

0.85

Older

3 (2%)

4 (6%)

30 (8%)

11 (7%)

0 (0%)

0.19

Oldest

0 (0%)

1 (4%)

16 (7%)

6 (8%)

0 (0%)

0.32

Signature 12

Total

10 (7%)

6 (9%)

59 (14%)

17 (9%)

3 (14%)

0.14

Unknown

Young

0 (0%)

0 (0%)

5 (13%)

1 (6%)

0 (0%)

0.53

Older

10 (8%)

6 (9%)

54 (14%)

16 (10%)

3 (14%)

0.31

Oldest

4 (9%)

2 (7%)

34 (16%)

8 (11%)

2 (33%)

0.29

Signature 13

Total

50 (34%)

42 (61%)

113 (26%)

46 (25%)

9 (41%)

< 0.01*

AID/APOBEC

Young

5 (29%)

2 (67%)

8 (21%)

2 (11%)

1 (100%)

0.07

Older

45 (35%)

40 (61%)

105 (27%)

44 (27%)

8 (38%)

< 0.01*

Oldest

16 (36%)

15 (56%)

57 (26%)

16 (21%)

3 (50%)

< 0.01*

Signature 14

Total

2 (1%)

0 (0%)

8 (2%)

9 (5%)

0 (0%)

0.13

Unknown

Young

0 (0%)

0 (0%)

4 (11%)

4 (22%)

0 (0%)

0.27

Older

2 (2%)

0 (0%)

4 (1%)

5 (3%)

0 (0%)

0.38

Oldest

0 (0%)

0 (0%)

1 (0%)

4 (5%)

0 (0%)

0.05

Signature 15

Total

18 (12%)

9 (13%)

74 (17%)

31 (17%)

3 (14%)

0.65

Defective DNA mismatch repair

Young

1 (6%)

0 (0%)

9 (24%)

2 (11%)

0 (0%)

0.43

Older

17 (13%)

9 (14%)

65 (17%)

29 (18%)

3 (14%)

0.84

Oldest

8 (18%)

4 (15%)

33 (15%)

15 (20%)

0 (0%)

0.77

Signature 16

Total

15 (10%)

9 (13%)

105 (24%)

37 (20%)

4 (18%)

< 0.01*

Unknown

Young

4 (24%)

0 (0%)

12 (32%)

2 (11%)

0 (0%)

0.48

Older

11 (9%)

9 (14%)

93 (24%)

35 (21%)

4 (19%)

< 0.01*

Oldest

4 (9%)

4 (15%)

48 (22%)

16 (21%)

1 (17%)

0.30

Signature 17

Total

2 (1%)

2 (3%)

8 (2%)

4 (2%)

0 (0%)

0.89

Unknown

Young

1 (6%)

0 (0%)

1 (3%)

0 (0%)

0 (0%)

0.53

Older

1 (1%)

2 (3%)

7 (2%)

4 (2%)

0 (0%)

0.71

Oldest

0 (0%)

0 (0%)

2 (1%)

3 (4%)

0 (0%)

0.23

Signature 18

Total

8 (5%)

2 (3%)

50 (12%)

14 (8%)

3 (14%)

0.03*

Unknown

Young

0 (0%)

0 (0%)

5 (13%)

1 (6%)

0 (0%)

0.53

Older

8 (6%)

2 (3%)

45 (12%)

13 (8%)

3 (14%)

0.08

Oldest

2 (4%)

1 (4%)

26 (12%)

4 (5%)

0 (0%)

0.28

Signature 19

Total

8 (5%)

4 (6%)

37 (9%)

14 (8%)

0 (0%)

0.55

Unknown

Young

1 (6%)

1 (33%)

1 (3%)

1 (6%)

0 (0%)

0.22

Older

7 (5%)

3 (5%)

36 (9%)

13 (8%)

0 (0%)

0.40

Oldest

4 (9%)

1 (4%)

21 (10%)

5 (7%)

0 (0%)

0.87

Signature 20

Total

8 (5%)

1 (1%)

13 (3%)

7 (4%)

1 (5%)

0.51

Defective DNA mismatch repair

Young

2 (12%)

0 (0%)

1 (3%)

0 (0%)

0 (0%)

0.31

Older

6 (5%)

1 (2%)

12 (3%)

7 (4%)

1 (5%)

0.66

Oldest

5 (11%)

1 (4%)

8 (4%)

4 (5%)

0 (0%)

0.30

Signature 21

Total

4 (3%)

1 (1%)

22 (5%)

5 (3%)

0 (0%)

0.46

Unknown

Young

0 (0%)

0 (0%)

3 (8%)

1 (6%)

0 (0%)

0.84

Older

4 (3%)

1 (2%)

19 (5%)

4 (2%)

0 (0%)

0.58

Oldest

3 (7%)

0 (0%)

10 (5%)

0 (0%)

0 (0%)

0.16

Signature 22

Total

3 (2%)

2 (3%)

47 (11%)

10 (5%)

2 (9%)

< 0.01*

Aristolochic acid

Young

0 (0%)

0 (0%)

6 (16%)

1 (6%)

0 (0%)

0.37

Older

3 (2%)

2 (3%)

41 (10%)

9 (5%)

2 (10%)

< 0.01*

Oldest

1 (2%)

1 (4%)

23 (11%)

2 (3%)

0 (0%)

0.11

Signature 23

Total

1 (1%)

1 (1%)

14 (3%)

3 (2%)

0 (0%)

0.44

Unknown

Young

0 (0%)

0 (0%)

0 (0%)

1 (6%)

0 (0%)

0.51

Older

1 (1%)

1 (2%)

14 (4%)

2 (1%)

0 (0%)

0.35

Oldest

0 (0%)

0 (0%)

7 (3%)

2 (3%)

0 (0%)

0.79

Signature 24

Total

17 (12%)

7 (10%)

55 (13%)

20 (11%)

4 (18%)

0.81

Aflatoxin

Young

7 (41%)

0 (0%)

3 (8%)

1 (6%)

0 (0%)

0.02*

Older

10 (8%)

7 (11%)

52 (13%)

19 (12%)

4 (19%)

0.38

Oldest

3 (7%)

3 (11%)

36 (16%)

6 (8%)

1 (17%)

0.21

Signature 25

Total

13 (9%)

4 (6%)

54 (13%)

12 (7%)

3 (14%)

0.11

Unknown

Young

1 (6%)

0 (0%)

3 (8%)

2 (11%)

0 (0%)

0.90

Older

12 (9%)

4 (6%)

51 (13%)

10 (6%)

3 (14%)

0.08

Oldest

3 (7%)

1 (4%)

35 (16%)

4 (5%)

0 (0%)

0.05*

Signature 26

Total

12 (8%)

2 (3%)

30 (7%)

12 (7%)

2 (9%)

0.63

Defective DNA mismatch repair

Young

0 (0%)

0 (0%)

1 (3%)

0 (0%)

0 (0%)

1.00

Older

12 (9%)

2 (3%)

29 (7%)

12 (7%)

2 (10%)

0.56

Oldest

7 (16%)

0 (0%)

14 (6%)

8 (11%)

0 (0%)

0.11

Signature 27

Total

1 (1%)

0 (0%)

6 (1%)

0 (0%)

2 (9%)

0.03*

Unknown

Young

0 (0%)

0 (0%)

0 (0%)

0 (0%)

0 (0%)

1.00

Older

1 (1%)

0 (0%)

6 (2%)

0 (0%)

2 (10%)

0.03*

Oldest

0 (0%)

0 (0%)

4 (2%)

0 (0%)

0 (0%)

0.84

Signature 28

Total

2 (1%)

2 (3%)

14 (3%)

2 (1%)

0 (0%)

0.48

Unknown

Young

0 (0%)

0 (0%)

0 (0%)

0 (0%)

0 (0%)

1.00

Older

2 (2%)

2 (3%)

14 (4%)

2 (1%)

0 (0%)

0.50

Oldest

0 (0%)

2 (7%)

6 (3%)

2 (3%)

0 (0%)

0.42

Signature 29

Total

19 (13%)

10 (14%)

92 (21%)

32 (18%)

4 (18%)

0.19

Chewing tobacco

Young

0 (0%)

1 (33%)

4 (11%)

6 (33%)

0 (0%)

0.03*

Older

19 (15%)

9 (14%)

88 (23%)

26 (16%)

4 (19%)

0.15

Oldest

8 (18%)

4 (15%)

46 (21%)

10 (13%)

3 (50%)

0.20

Signature 30

Total

18 (12%)

2 (3%)

58 (14%)

20 (11%)

4 (18%)

0.07

Unknown

Young

5 (29%)

1 (33%)

3 (8%)

0 (0%)

0 (0%)

0.03*

Older

13 (10%)

1 (2%)

55 (14%)

20 (12%)

4 (19%)

0.01*

Oldest

6 (13%)

0 (0%)

29 (13%)

11 (15%)

1 (17%)

0.22

Total

Total

146 (100%)

69 (100%)

429 (100%)

182 (100%)

22 (100%)

 

Young

17 (100%)

3 (100%)

38 (100%)

18 (100%)

1 (100%)

Older

129 (100%)

66 (100%)

391 (100%)

164 (100%)

21 (100%)

Oldest

45 (100%)

27 (100%)

219 (100%)

75 (100%)

6 (100%)

  1. Frequency and proportion of breast tumours of each PAM50 tumour type with each COSMIC signature present. Entries are number of samples with each signature present above a threshold of 6% (% of tumours of each PAM50 subtype). Signatures were identified using R package “deconstructSigs”. The p-values were calculated using a Fisher’s exact test (* indicates statistical significance at the 0.05 level). COSMIC: Catalogue Of Somatic Mutations In Cancer; HER2+: human epidermal growth factor receptor 2 over-expressing; PAM50: prediction analysis of microarrays 50 gene set
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