A pan-cancer analysis of driver gene mutations, DNA methylation and gene expressions reveals that chromatin remodeling is a major mechanism inducing global changes in cancer epigenomes

Table 2 MDGs dysregulate expression levels of chromatin regulators

MDGs	\|T_i\|	N₁ (# of dysregulated genes)	N₂ (# of dysregulated genes in list A)	Enrichment Pvalue_A	N₃ (# of dysregulated genes in list B)	Enrichment Pvalue_B	Genes in list B that are dysregulated^a	Genes in list B that are differentially methylated^b
TP53	8	233	19	0.00056	5	3.2e-06	CBX7 RAD54L TTF2 KDM1A SUV39H2
PTEN	3	1,534	81	0.00012	9	9.1e-06	DNMT1 DNMT3A SETBP1 PRDM5 CBX7 RAD54L EZH2 PCNA HDAC1	DNMT3A PRDM5 HDAC1
RB1	2	1,447	83	5.2e-06	4	0.056	DNMT1 EYA4 EZH2 PCNA	PCNA
NF1	2	766	36	0.044	0	1
CTNNB1	2	5,515	207	0.12	12	0.0033	DNMT1 SETBP1 PRDM2 PRDM5 CBX7 KAT2B RAD54L WHSC1 EZH2 UHRF1 TDG TET3	PRDM2 CBX7
HRAS	2	1,137	63	2.0e-04	3	0.11	PRDM2 RAD54L HDAC1	PRDM2
BRAF	2	3,128	133	0.008	8	0.0091	DNMT1 DNMT3A DNMT3B KAT2B WHSC1 EZH2 UHRF1 KDM1A	DNMT3A UHRF1
IDH1	2	3,560	208	2.8e-15	2	0.9	SUV39H2 TET3
NRAS	2	1,609	87	2.8e-05	1	0.82	HDAC1
RNF43	2	3,212	157	4.4e-06	8	0.011	DNMT3A DNMT3B PRDM2 RAD54L WHSC1 UHRF1 HDAC1 TET3	DNMT3A DNMT3B PRDM2 WHSC1
ZBTB20	2	1,563	78	0.00088	6	0.0039	DNMT3A RAD54L WHSC1 UHRF1 TTF2 HDAC1	DNMT3A WHSC1 UHRF11
CDH1	2	2,792	136	2.7e-05	14	3.3e-08	DNMT3B SETBP1 PRDM2 CBX7 DUSP1 RAD54L WHSC1 EZH2 PCNA KDM1A SUV39H2 HDAC1 TDG TET3	PRDM2 CBX7 WHSC1 KDM1A

|Ti|: number of tumor types whose genome-wide methylation levels are significantly associated with the mutation status of CDG i;
N₁: number of genes whose expression levels are dysregulated by MDG i in all |Ti| tumor types;
N₂: number of genes in list A that are dysregulated in all |Ti| tumor types;
N₃: number of genes in list B that are dysregulated in all |Ti| tumor types;
Enrichment Pvalue_A, and Pvalue_B are calculated using hypergeometric distributions testing if genes in lists A and B are enriched among genome-wide differentially expressed target genes;
^aGenes in list B that are dysregulated in all |Ti| tumor types;
^bGenes in list B that are differentially methylated in all |Ti| tumor types.

ISSN: 1755-8794