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 4 Identified 29 EDGs

EDGs	∣A′_i∣	∣E_i∣	p′_i	B _i	\( {E}_i^{-} \)	\( {E}_i^{+} \)
TP53	14	11	< e-06	both	HNSC LGG SARC	BLCA BRCA COAD GBM KIRC LIHC LUAD STAD
PTEN	14	1	0.00299	up		LGG
PIK3CA	11	2	0.00536	down	BRCA STAD
RB1	10	3	9e-05	up		BLCA LGG LUAD
ARID1A	10	2	0.00557	both	STAD	CESC
KRAS	8	4	4e-06	down	COAD LUAD PAAD TGCT
KMT2D	8	1	0.0265	down	STAD
NF1	6	1	0.00274	up		LGG
CTNNB1	5	1	0.00572	down	LIHC
†SETD2	5	0	0.00833	NA	NA	NA
BRAF	4	2	1.1e-05	down	COAD THCA
EGFR	4	2	5.3e-05	up		LGG LUAD
HRAS	4	3	7e-05	down	HNSC PCPG THCA
CIC	3	1	< e-06	down	LGG
IDH1	3	2	< e-06	both	LGG	GBM
RNF43	3	2	1e-06	down	COAD STAD
ATRX	3	2	2e-06	both	LGG	GBM
CDH1	3	2	7e-06	both	BRCA	STAD
NRAS	3	2	0.000199	up		TGCT THCA
KEAP1	3	1	0.000809	down	LUAD
ZBTB20	3	2	0.00119	down	COAD STAD
NOTCH1	3	2	0.00182	down	HNSC LGG
SMARCA4	3	1	0.0108	up		LUAD
GATA3 ^a	3	1	0.0138	down	BRCA
KMT2B	2	2	0.000317	down	COAD STAD
KIT	2	1	0.000889	down	TGCT
FUBP1 ^a	1	1	< e-06	down	LGG
SPOP ^a	1	1	< e-06	down	PRAD
NSD1	1	1	0.000432	up		HNSC

∣A′_i∣ = number of tumor types in which EDG i is mutated in ≥ 5 samples with expression data;
∣E_i∣ = number of tumor types whose genome-wide expression levels are significantly associated with CDG i;
\( {p}_i^{\prime }= \) p-value testing if CDG i is significantly associated with genome-wide expression changes across tumor types;
Bi is the direction of change of expression levels associated with the mutation status of CDG i;
\( {E}_i^{+}= \) tumor types that are up-regulated by CDG i, \( {E}_i^{-} \)= tumor types that are down-regulated by CDG i;
^a : genes that are not overlapping driver genes.
†Note that SETD2 gene has a significant p-value \( {p}_i^{\prime } \) for testing association of genome-wide expression changes across multiple tumor types, but there is not a specific tumor type in which SETD2 mutation is significantly associated with genome-wide expression changes.

ISSN: 1755-8794