CpG island methylator phenotype in adenocarcinomas from the digestive tract: Methods, conclusions, and controversies

Table 6 Genes differentially mutated between CpG island methylator phenotype+ and CpG island methylator phenotype- gastrointestinal adenocarcinoma samples¹

Gene	Count CIMP+	% CIMP+	Count CIMP-	% CIMP-	P% Diff	P-value	FDR	Pathway
KMT2D	35	20.30%	10	4.30%	16.00%	6.22E-07	2.24E-05	Chromatin
ARID1A	60	34.90%	32	13.90%	21.00%	1.15E-06	2.24E-05	Chromatin
RNF43	42	24.40%	17	7.40%	17.10%	3.04E-06	3.79E-05	Wnt
CSF3R	19	11.00%	2	0.90%	10.20%	4.19E-06	3.79E-05	ERK
SOX7	14	8.10%	0	0.00%	8.10%	4.86E-06	3.79E-05	ERK
PIK3CA	48	27.90%	26	11.30%	16.70%	2.62E-05	1.70E-04	PI3K/RAS
PAX6	17	9.90%	2	0.90%	9.00%	3.96E-05	2.21E-04	Differentiation
ATM	37	21.50%	17	7.40%	14.20%	5.05E-05	2.46E-04	DNA damage
KRAS	52	30.20%	32	13.90%	16.40%	1.04E-04	4.53E-04	PI3K/RAS
EGR1	15	8.70%	2	0.90%	7.90%	1.63E-04	6.37E-04	Differentiation
GATA3	19	11.00%	5	2.20%	8.90%	2.22E-04	7.87E-04	NF-KB
KMT2C	38	22.10%	22	9.50%	12.60%	6.15E-04	2.00E-03	Chromatin
ALDH2	10	5.80%	1	0.40%	5.40%	1.18E-03	3.30E-03	Metabolic
CDK12	18	10.50%	6	2.60%	7.90%	1.18E-03	3.30E-03	PI3K/RAS
SAFB	15	8.70%	4	1.70%	7.00%	1.44E-03	3.73E-03	Chromatin
BCOR	19	11.00%	7	3.00%	8.00%	1.68E-03	4.09E-03	Chromatin
PTEN	24	14.00%	11	4.80%	9.20%	1.97E-03	4.32E-03	PI3K/RAS
AXIN2	21	12.20%	9	3.90%	8.30%	2.00E-03	4.32E-03	Wnt
CTCF	14	8.10%	4	1.70%	6.40%	2.73E-03	5.41E-03	Chromatin
PALB2	11	6.40%	2	0.90%	5.50%	2.77E-03	5.41E-03	DNA repair
ERBB3	18	10.50%	7	3.00%	7.40%	2.96E-03	5.49E-03	PI3K/RAS
ERBB4	29	16.90%	17	7.40%	9.50%	4.05E-03	6.97E-03	PI3K/RAS
FBXW7	32	18.60%	20	8.70%	9.90%	4.11E-03	6.97E-03	Notch
CIC	23	13.40%	12	5.20%	8.20%	6.55E-03	1.06E-02	Proliferation
HLA.A	17	9.90%	8	3.50%	6.40%	1.13E-02	1.71E-02	Immune
MSH6	19	11.00%	10	4.30%	6.70%	1.14E-02	1.71E-02	MMR
ERBB2	15	8.70%	8	3.50%	5.30%	2.98E-02	4.21E-02	PI3K/RAS
CASP8	13	7.60%	6	2.60%	5.00%	3.02E-02	4.21E-02	Apoptosis
SMAD4	27	15.70%	20	8.70%	7.00%	4.05E-02	5.45E-02	Wnt
TFE3	6	3.50%	1	0.40%	3.10%	4.53E-02	5.90E-02	Wnt
APC	82	47.70%	87	37.70%	10.00%	5.24E-02	6.60E-02	Wnt
NRAS	10	5.80%	5	2.20%	3.60%	6.55E-02	7.74E-02	PI3K/RAS
SMARCB1	10	5.80%	5	2.20%	3.60%	6.55E-02	7.74E-02	Chromatin
IGFBP7	3	1.70%	0	0.00%	1.70%	7.70E-02	8.65E-02	DNA Damage
TBL1XR1	6	3.50%	2	0.90%	2.60%	7.76E-02	8.65E-02	Wnt

¹Results are based on a combined set of 179 CIMP- and 154 CIMP+ gastrointestinal adenocarcinoma samples. P-values were computed using a two-tailed Fishers’ exact test. Only genes with FDR < 10% are shown. CIMP: CpG island methylator phenotype.