Table 2 Canonical pathways represented among the top 10% of decreased and increased methylated genes from differentially methylated regions in germinoma relative to yolk sac tumours (p-values < 0.01)

From: Differences in DNA methylation profiles by histologic subtype of paediatric germ cell tumours: a report from the Children’s Oncology Group

IPA pathway	Genes	p-value
Decreased methylation in germinoma^a compared to YST
TWEAK signalling	TRAF3, TRAF2, TNFSF12, CASP8, CASP7, TRAF1	0.0001
Cardiac hypertrophy signalling	ADCY3, RHOT2, HAND1, ADRB3, PIK3R3, NKX2–5, PLCD3, CACNA1E, GNAO1, PRKACA, GNB2, IGF1R, PIK3CD, GNB1L, FNBP1	0.0001
Tec kinase signalling	PTK2, PIK3R3, TNFSF12, GNAO1, RHOT2, GNB2, PIK3CD, JAK3, GNB1L, TNF, FNBP1, PRKCZ	0.0001
Sphingosine-1-phosphate signalling	PTK2, PIK3R3, PLCD3, PDGFA, ADCY3, RHOT2, PIK3CD, CASP8, FNBP1, CASP7	0.0002
Cytotoxic T lymphocyte-mediated apoptosis of target cells	CD247, B2M, HLA-A, CASP8, CASP7	0.0004
Role of NFAT in cardiac hypertrophy	PIK3R3, PLCD3, NKX2–5, HDAC7, ADCY3, GNB2, PRKACA, IGF1R, HAND1, PIK3CD, GNB1L, PRKCZ	0.0004
Molecular mechanisms of cancer	RAPGEF1, RHOT2, ADCY3, PRKCZ, PIK3R3, PTK2, NF1, CDK20, GNAO1, E2F1, PRKACA, PIK3CD, CASP8, JAK3, NOTCH1, FNBP1, CASP7, LRP1	0.001
NF-κB signalling	PIK3R3, TRAF3, TRAF2, PRKACA, IGF1R, PIK3CD, LTBR, CASP8, TNFRSF1B, TNF, PRKCZ	0.001
Role of macrophages, fibroblasts and endothelial cells in rheumatoid arthritis	TRAF3, PDGFA, PRKCZ, PIK3R3, PLCD3, TRAF2, APC2, GNAO1, PIK3CD, LTBR, SOST, TNFRSF1B, TNF, LRP1, TRAF1	0.001
RAR activation	PIK3R3, PRMT2, CSK, NR2F2, ADCY3, PRKACA, PIK3CD, NCOR2, PML, PRKCZ, SMARCA4	0.001
Huntington’s disease signalling	SDHA, PRKCZ, PIK3R3, DNAJC5, HDAC7, GNB2, IGF1R, VAMP3, PIK3CD, NCOR2, CASP8, GNB1L, CASP7	0.001
Small-cell lung cancer signalling	PTK2, PIK3R3, TRAF3, TRAF2, E2F1, PIK3CD, TRAF1	0.001
Type I diabetes mellitus signalling	CD247, CD28, TRAF2, HLA-A, GAD1, CASP8, TNFRSF1B, TNF	0.002
CXCR4 signalling	PTK2, PIK3R3, GNAO1, ADCY3, RHOT2, GNB2, PIK3CD, GNB1L, FNBP1, PRKCZ	0.002
Lymphotoxin β-receptor signalling	PIK3R3, TRAF3, TRAF2, PIK3CD, LTBR, TRAF1	0.002
Death receptor signalling	TRAF2, TNFSF12, LMNA, CASP8, TNFRSF1B, TNF, CASP7	0.002
Thrombin signalling	PTK2, PIK3R3, PLCD3, GNAO1, ADCY3, RHOT2, GNB2, PIK3CD, GNB1L, FNBP1, PRKCZ	0.002
Myc-mediated apoptosis signalling	PIK3R3, YWHAG, IGF1R, PIK3CD, CASP8, PRKCZ	0.002
TNFR2 signalling	TRAF2, TNFRSF1B, TNF, TRAF1	0.003
Colorectal cancer metastasis signalling	PIK3R3, GRK2, ADCY3, RHOT2, GNB2, PRKACA, PIK3CD, JAK3, GNB1L, TNF, FNBP1, LRP1	0.004
CREB signalling in neurons	PIK3R3, PLCD3, GRM3, GNAO1, ADCY3, GNB2, PRKACA, PIK3CD, GNB1L, PRKCZ	0.004
Relaxin signalling	PIK3R3, PDE9A, GNAO1, ADCY3, GNB2, PRKACA, PIK3CD, GNB1L, PRKCZ	0.004
Gαq signalling	PIK3R3, GRK2, CSK, RHOT2, GNB2, PIK3CD, GNB1L, FNBP1, PRKCZ	0.004
CD40 signalling	PIK3R3, TRAF3, TRAF2, PIK3CD, JAK3, TRAF1	0.004
Glioblastoma multiforme signalling	PIK3R3, PLCD3, NF1, PDGFA, E2F1, RHOT2, IGF1R, PIK3CD, FNBP1	0.005
IGF-1 signalling	PTK2, PIK3R3, YWHAG, PRKACA, IGF1R, PIK3CD, PRKCZ	0.005
P2Y purigenic receptor signalling pathway	PIK3R3, PLCD3, ADCY3, GNB2, PRKACA, PIK3CD, GNB1L, PRKCZ	0.005
Antigen presentation pathway	B2M, PSMB9, HLA-A, TAP1	0.006
Cardiac β-adrenergic Signalling	CACNA1E, GRK2, PDE9A, PPP1R3C, ADCY3, GNB2, PRKACA, GNB1L	0.006
Induction of apoptosis by HIV1	TRAF2, CASP8, TNFRSF1B, TNF, TRAF1	0.007
Role of PKR in interferon induction and antiviral response	TRAF3, TRAF2, CASP8, TNF	0.008
Increased methylation in germinoma relative to YST
Axonal guidance signalling	NTNG1, EFNB2, SRGAP3, BMP4, GLIS1, ARHGEF7, GNA12, C9orf3, ADAM19, PFN2, HHIP, KLB, GNG7, PRKCB	0.0005
Signalling by Rho family GTPases	MAP3K9, CDH1, GNA12, ARHGEF7, PIP4K2B, ARHGEF18, ARHGEF3, KLB, GNG7	0.002
Breast cancer regulation by stathmin1	CAMK1D, ARHGEF7, ARHGEF18, ITPR1, ARHGEF3, KLB, GNG7, PRKCB	0.002
RhoGDI signalling	CDH1, GNA12, ARHGEF7, PIP4K2B, ARHGEF18, ARHGEF3, GNG7	0.003
TR/RXR activation	F10, PDE3B, PFKP, THRB, KLB	0.004
Coagulation system	F10, F3, SERPINF2	0.006
Thrombin signalling	CAMK1D, GNA12, ITPR1, ARHGEF3, KLB, GNG7, PRKCB	0.007
Guanosine nucleotides degradation III	NT5C2, ACPP	0.007
Relaxin signalling	PDE3B, GNA12, PDE4D, NPR2, KLB, GNG7	0.007
Urate biosynthesis/inosine 5’-phosphate degradation	NT5C2, ACPP	0.009

^aGerminoma includes germinoma, seminoma and dysgerminoma

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Table 2 Canonical pathways represented among the top 10% of decreased and increased methylated genes from differentially methylated regions in germinoma relative to yolk sac tumours (p-values < 0.01)

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