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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

SignatureAge groupBasal-likeHER2+Luminal ALuminal BNormal-likep-valueProposed Etiology
Signature 1Total107 (73%)56 (81%)330 (77%)139 (76%)14 (64%)0.45Spontaneous deamination of 5-methylcytosine
Young14 (82%)2 (67%)28 (74%)11 (61%)1 (100%)0.65
Older93 (72%)54 (82%)302 (77%)128 (78%)13 (62%)0.27
Oldest36 (80%)20 (74%)175 (80%)61 (81%)4 (67%)0.80
Signature 2Total28 (19%)47 (68%)169 (39%)59 (32%)8 (36%)< 0.01*AID/APOBEC
Young3 (18%)2 (67%)14 (37%)2 (11%)1 (100%)0.04*
Older25 (19%)45 (68%)155 (40%)57 (35%)7 (33%)< 0.01*
Oldest12 (27%)19 (70%)82 (37%)22 (29%)3 (50%)< 0.01*
Signature 3Total134 (92%)46 (67%)252 (59%)136 (75%)15 (68%)< 0.01*Defective DNA double-strand break repair by homologous recombination
Young17 (100%)1 (33%)20 (53%)14 (78%)1 (100%)< 0.01*
Older117 (91%)45 (68%)232 (59%)122 (74%)14 (67%)< 0.01*
Oldest41 (91%)18 (67%)125 (57%)55 (73%)3 (50%)< 0.01*
Signature 4Total26 (18%)4 (6%)48 (11%)24 (13%)3 (14%)0.11Smoking tobacco
Young3 (18%)1 (33%)6 (16%)5 (28%)0 (0%)0.60
Older23 (18%)3 (5%)42 (11%)19 (12%)3 (14%)0.07
Oldest7 (16%)2 (7%)24 (11%)8 (11%)1 (17%)0.75
Signature 5Total17 (12%)18 (26%)145 (34%)50 (27%)3 (14%)< 0.01*Unknown
Young1 (6%)0 (0%)13 (34%)7 (39%)0 (0%)0.08
Older16 (12%)18 (27%)132 (34%)43 (26%)3 (14%)< 0.01*
Oldest4 (9%)9 (33%)82 (37%)19 (25%)2 (33%)< 0.01*
Signature 6Total23 (16%)7 (10%)61 (14%)25 (14%)1 (5%)0.64Defective DNA mismatch repair
Young3 (18%)0 (0%)8 (21%)4 (22%)0 (0%)1.00
Older20 (16%)7 (11%)53 (14%)21 (13%)1 (5%)0.75
Oldest4 (9%)4 (15%)34 (16%)10 (13%)0 (0%)0.78
Signature 7Total15 (10%)17 (25%)98 (23%)30 (16%)5 (23%)< 0.01*UV light
Young2 (12%)1 (33%)6 (16%)2 (11%)0 (0%)0.75
Older13 (10%)16 (24%)92 (24%)28 (17%)5 (24%)< 0.01*
Oldest4 (9%)5 (19%)51 (23%)8 (11%)2 (33%)0.03*
Signature 8Total27 (18%)11 (16%)86 (20%)39 (21%)4 (18%)0.90Unknown
Young5 (29%)3 (100%)5 (13%)5 (28%)0 (0%)0.02*
Older22 (17%)8 (12%)81 (21%)34 (21%)4 (19%)0.51
Oldest6 (13%)3 (11%)52 (24%)17 (23%)1 (17%)0.38
Signature 9Total24 (16%)9 (13%)63 (15%)34 (19%)6 (27%)0.38Polymerase η
Young2 (12%)0 (0%)6 (16%)4 (22%)0 (0%)0.88
Older22 (17%)9 (14%)57 (15%)30 (18%)6 (29%)0.38
Oldest9 (20%)4 (15%)35 (16%)16 (21%)0 (0%)0.69
Signature 10Total5 (3%)2 (3%)25 (6%)11 (6%)3 (14%)0.28Defective polymerase POLE
Young1 (6%)0 (0%)0 (0%)0 (0%)0 (0%)0.27
Older4 (3%)2 (3%)25 (6%)11 (7%)3 (14%)0.20
Oldest1 (2%)2 (7%)12 (5%)4 (5%)1 (17%)0.48
Signature 11Total5 (3%)4 (6%)33 (8%)13 (7%)0 (0%)0.34Alkylating agents (e.g. temozolomide)
Young2 (12%)0 (0%)3 (8%)2 (11%)0 (0%)0.85
Older3 (2%)4 (6%)30 (8%)11 (7%)0 (0%)0.19
Oldest0 (0%)1 (4%)16 (7%)6 (8%)0 (0%)0.32
Signature 12Total10 (7%)6 (9%)59 (14%)17 (9%)3 (14%)0.14Unknown
Young0 (0%)0 (0%)5 (13%)1 (6%)0 (0%)0.53
Older10 (8%)6 (9%)54 (14%)16 (10%)3 (14%)0.31
Oldest4 (9%)2 (7%)34 (16%)8 (11%)2 (33%)0.29
Signature 13Total50 (34%)42 (61%)113 (26%)46 (25%)9 (41%)< 0.01*AID/APOBEC
Young5 (29%)2 (67%)8 (21%)2 (11%)1 (100%)0.07
Older45 (35%)40 (61%)105 (27%)44 (27%)8 (38%)< 0.01*
Oldest16 (36%)15 (56%)57 (26%)16 (21%)3 (50%)< 0.01*
Signature 14Total2 (1%)0 (0%)8 (2%)9 (5%)0 (0%)0.13Unknown
Young0 (0%)0 (0%)4 (11%)4 (22%)0 (0%)0.27
Older2 (2%)0 (0%)4 (1%)5 (3%)0 (0%)0.38
Oldest0 (0%)0 (0%)1 (0%)4 (5%)0 (0%)0.05
Signature 15Total18 (12%)9 (13%)74 (17%)31 (17%)3 (14%)0.65Defective DNA mismatch repair
Young1 (6%)0 (0%)9 (24%)2 (11%)0 (0%)0.43
Older17 (13%)9 (14%)65 (17%)29 (18%)3 (14%)0.84
Oldest8 (18%)4 (15%)33 (15%)15 (20%)0 (0%)0.77
Signature 16Total15 (10%)9 (13%)105 (24%)37 (20%)4 (18%)< 0.01*Unknown
Young4 (24%)0 (0%)12 (32%)2 (11%)0 (0%)0.48
Older11 (9%)9 (14%)93 (24%)35 (21%)4 (19%)< 0.01*
Oldest4 (9%)4 (15%)48 (22%)16 (21%)1 (17%)0.30
Signature 17Total2 (1%)2 (3%)8 (2%)4 (2%)0 (0%)0.89Unknown
Young1 (6%)0 (0%)1 (3%)0 (0%)0 (0%)0.53
Older1 (1%)2 (3%)7 (2%)4 (2%)0 (0%)0.71
Oldest0 (0%)0 (0%)2 (1%)3 (4%)0 (0%)0.23
Signature 18Total8 (5%)2 (3%)50 (12%)14 (8%)3 (14%)0.03*Unknown
Young0 (0%)0 (0%)5 (13%)1 (6%)0 (0%)0.53
Older8 (6%)2 (3%)45 (12%)13 (8%)3 (14%)0.08
Oldest2 (4%)1 (4%)26 (12%)4 (5%)0 (0%)0.28
Signature 19Total8 (5%)4 (6%)37 (9%)14 (8%)0 (0%)0.55Unknown
Young1 (6%)1 (33%)1 (3%)1 (6%)0 (0%)0.22
Older7 (5%)3 (5%)36 (9%)13 (8%)0 (0%)0.40
Oldest4 (9%)1 (4%)21 (10%)5 (7%)0 (0%)0.87
Signature 20Total8 (5%)1 (1%)13 (3%)7 (4%)1 (5%)0.51Defective DNA mismatch repair
Young2 (12%)0 (0%)1 (3%)0 (0%)0 (0%)0.31
Older6 (5%)1 (2%)12 (3%)7 (4%)1 (5%)0.66
Oldest5 (11%)1 (4%)8 (4%)4 (5%)0 (0%)0.30
Signature 21Total4 (3%)1 (1%)22 (5%)5 (3%)0 (0%)0.46Unknown
Young0 (0%)0 (0%)3 (8%)1 (6%)0 (0%)0.84
Older4 (3%)1 (2%)19 (5%)4 (2%)0 (0%)0.58
Oldest3 (7%)0 (0%)10 (5%)0 (0%)0 (0%)0.16
Signature 22Total3 (2%)2 (3%)47 (11%)10 (5%)2 (9%)< 0.01*Aristolochic acid
Young0 (0%)0 (0%)6 (16%)1 (6%)0 (0%)0.37
Older3 (2%)2 (3%)41 (10%)9 (5%)2 (10%)< 0.01*
Oldest1 (2%)1 (4%)23 (11%)2 (3%)0 (0%)0.11
Signature 23Total1 (1%)1 (1%)14 (3%)3 (2%)0 (0%)0.44Unknown
Young0 (0%)0 (0%)0 (0%)1 (6%)0 (0%)0.51
Older1 (1%)1 (2%)14 (4%)2 (1%)0 (0%)0.35
Oldest0 (0%)0 (0%)7 (3%)2 (3%)0 (0%)0.79
Signature 24Total17 (12%)7 (10%)55 (13%)20 (11%)4 (18%)0.81Aflatoxin
Young7 (41%)0 (0%)3 (8%)1 (6%)0 (0%)0.02*
Older10 (8%)7 (11%)52 (13%)19 (12%)4 (19%)0.38
Oldest3 (7%)3 (11%)36 (16%)6 (8%)1 (17%)0.21
Signature 25Total13 (9%)4 (6%)54 (13%)12 (7%)3 (14%)0.11Unknown
Young1 (6%)0 (0%)3 (8%)2 (11%)0 (0%)0.90
Older12 (9%)4 (6%)51 (13%)10 (6%)3 (14%)0.08
Oldest3 (7%)1 (4%)35 (16%)4 (5%)0 (0%)0.05*
Signature 26Total12 (8%)2 (3%)30 (7%)12 (7%)2 (9%)0.63Defective DNA mismatch repair
Young0 (0%)0 (0%)1 (3%)0 (0%)0 (0%)1.00
Older12 (9%)2 (3%)29 (7%)12 (7%)2 (10%)0.56
Oldest7 (16%)0 (0%)14 (6%)8 (11%)0 (0%)0.11
Signature 27Total1 (1%)0 (0%)6 (1%)0 (0%)2 (9%)0.03*Unknown
Young0 (0%)0 (0%)0 (0%)0 (0%)0 (0%)1.00
Older1 (1%)0 (0%)6 (2%)0 (0%)2 (10%)0.03*
Oldest0 (0%)0 (0%)4 (2%)0 (0%)0 (0%)0.84
Signature 28Total2 (1%)2 (3%)14 (3%)2 (1%)0 (0%)0.48Unknown
Young0 (0%)0 (0%)0 (0%)0 (0%)0 (0%)1.00
Older2 (2%)2 (3%)14 (4%)2 (1%)0 (0%)0.50
Oldest0 (0%)2 (7%)6 (3%)2 (3%)0 (0%)0.42
Signature 29Total19 (13%)10 (14%)92 (21%)32 (18%)4 (18%)0.19Chewing tobacco
Young0 (0%)1 (33%)4 (11%)6 (33%)0 (0%)0.03*
Older19 (15%)9 (14%)88 (23%)26 (16%)4 (19%)0.15
Oldest8 (18%)4 (15%)46 (21%)10 (13%)3 (50%)0.20
Signature 30Total18 (12%)2 (3%)58 (14%)20 (11%)4 (18%)0.07Unknown
Young5 (29%)1 (33%)3 (8%)0 (0%)0 (0%)0.03*
Older13 (10%)1 (2%)55 (14%)20 (12%)4 (19%)0.01*
Oldest6 (13%)0 (0%)29 (13%)11 (15%)1 (17%)0.22
TotalTotal146 (100%)69 (100%)429 (100%)182 (100%)22 (100%) 
Young17 (100%)3 (100%)38 (100%)18 (100%)1 (100%)
Older129 (100%)66 (100%)391 (100%)164 (100%)21 (100%)
Oldest45 (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