Introduction
Materials and methods
Informatics
Statistics
Clinical information
Gene lists
Gene name | Pathway |
---|---|
FOS, JUN, MAP2K3, MAP2K4, MAPK8, MAPK8I-3, MAP3K1, MAP3K7, TNF, MAPK3, MAPK6, MAPK12, MAPK13, MAPK14, MAPK9, MST1, MAP4K1, MAP2K7, MAP2K2, MAP2K6, MAP3K4 | MAPK |
CASP8, CHUK, IKBKB, IL1B, MAP4K4, NFKB1, NFKB2, NFRKB, REL, IRAK1 | NFkB |
CD4, CREBBP, CTLA4, FASLG, IL15, JAK2, LAG3, MAPK8, TGFB3, TNFRSF8, TNFRSF9, TYK2, CD27, CD40LG, CD80, PTPRC, CCR5, CXCR3, IL12B, IL12RB2, IL18R1, IL1RL1, IL27, IL7R, STAT1, STAT4, TBX21, TLR4, CCL11, CCL5, CCL7, CCR4, GATA3, GF1I, ICOS, IL13RA1, IL1R1, IL25, IRF4, JAK1, MAF, NFATC1, NFATC2, PCGF2 | T-cell regulation |
Base excision repair (BER) | DDR pathway |
---|---|
APEX1, APEX2, CCNO, FEN1, LIG3, MBD4, MPG, MUTYH, NEIL1, NEIL2, NEIL3, PARP1, PARP2, PARP3, PCNA, POLB, SMUG1, TDG, UNG, XRCC1 | Base excision repair (BER) |
ATXN3, CCNH, DDB1, DDB2, ERCC1, ERCC2, ERCC3, ERCC4, ERCC5, ERCC6, ERCC8, MMS19, PNKP, POLL, RAD23A, RAD23B, RPA1, RPA3, SLK, XAB2, XPA, XPC | Nucleotide excision repair (NER) |
MLH1, MLH3, MSH2, MSH3, MSH4, MSH5, MSH6, PMS1, PMS2, POLD3, TREX1 | Mismatch repair (MMR) |
ATM, BLM, BRCA2, DMC1, H2AFX, MUS81, POLD1, RAD51, RAD51C, RAD52, RAD54B, RAD54L, RPA2, TP53BP1 | Homologous recombination (HR) |
DLCRE1C, DNTT, LIG4, MRE11A, NBN, POLM, PRKDC, RAD50, XRCC2, XRCC5, XRCC6 | Non-homologous end joining (NHEJ) |
ABL1, ATR, BRIP1, CEP63, CHEK1, CHEK2, CHKA, CLSPN, DBF4, E2F1, FOXN3, GRP, HUS1B, MAD2L2, MAPK14, MYH1, PDP1, PIN4, PNPN11, RAD1, RFC4, TIPIN, TP53, WEE1, ZAK | DDR checkpoint |
ATRIP, ATRX, BARD1, BAX, BBC3, BRCA1, CDC25A, CDC25C, CDK7, CDKN1A, CIB1, CRY1, CSNK2A2, DDIT3, EXO1, FANCA, FANCD2, FANCG, GADD45A, GADD45G, LIG1, MAPK12, MCPH1, MDC1, MGMT, NTHL1, OGG1, PPM1D, PP1R15A, RAD17, RAD18, RAD21, RAD51B, RAD9A, RBBP8, REV1, RFC1, RNF168, RNF8, SIRT1, SMC1A, SUMO1, TOP3A, TOPSBP1, TP73, XRCC3, XRCC6BP1 | Multiple (Other) |
Results
Mutation load distribution is different between ER+ and ER− breast cancer
Characteristic | Mean | Standard deviation |
---|---|---|
Age at diagnosis (years) | 57.97 | 13.15 |
Mean mutation count (n) | 67.23 | 52.79 |
Mean overall survival (days) | 901.53 | 1069.441 |
Total number (n) | 762 | |
Tumor size at diagnosis (n) | ||
T1 | 201 | |
T2 | 441 | |
T3+ | 109 | |
Unknown | 11 | |
Nodal involvement at diagnosis (n) | ||
N0 | 364 | |
N1 | 249 | |
N2+ | 138 | |
Unknown | 11 | |
ER status of tumor (n) | ||
ER-positive | 559 | |
ER-negative | 165 | |
Triple-negative | 116 | |
Unknown | 38 | |
HER2 status of tumor (n) | ||
HER2-positive | 105 | |
HER2-negative | 621 | |
Unknown | 36 | |
Vital status of patient (n) | ||
Alive | 671 | |
Deceased | 91 |
SML associates with ER+ breast cancer survival
Factor | Hazard Ratio | CI |
p-Value |
---|---|---|---|
Mutation load | |||
LML | Ref. | ||
HML
|
2.02
|
1.02–4.00
|
0.04
|
HER2 status | |||
Negative | Ref. | ||
Positive | 1.65 | 0.66–4.12 | 0.29 |
PR status | |||
Negative | Ref. | ||
Positive | 0.55 | 0.25–1.24 | 0.15 |
Tumor stage | |||
Stage I | Ref. | ||
Stage II | 1.11 | 0.34–3.65 | 0.86 |
Stage III+ | 0.38 | 0.05–2.57 | 0.32 |
Nodal involvement | |||
N0 | Ref. | ||
N1 | 1.81 | 0.75–4.35 | 0.32 |
N2+
|
8.35
|
1.43–48.68
|
0.02
|
DNA damage repair pathways are mutated in tumors with HML
Mutations in known prognostic genes do not affect survival
Gene name | Mutational prognosis | Reference |
---|---|---|
GATA3 | Good | Ellis et al. [4] Nature |
MAP3K1 | Good | Ellis et al. [4] Nature |
MAP2K4 | Good | Ellis et al. [4] Nature |
PIK3CA | Good | Cizkova et al. [16] Br Canc Res |
CDKN1B | Poor | Depowski et al. [17] Mod Pathol |
RB1 | Poor | Ellis et al. [4] Nature |
PTEN | Poor | Alkarain et al. [18] J Mamm Gl Neopl |
TP53 | Poor | Ellis et al. [4] Nature |