BRAF mutation-specific promoter methylation of FOX genes in colorectal cancer

Clinical Epigenetics

Table 2 Pathways enriched for BRAF mutation-associated promoter methylation after exclusion of ES cell H3K27me ³ binding promoter regions

*BRAF* mutation-specific promoters (125)	Associated genes	Expected hits^a	Hits	P ^b
Hedgehog signaling pathway	SMO; GSK3A^c; CREBBP^c	0.16	3	0.000561
PI3 kinase pathway	FOXB1; FOXB2; FOXD3; CCND1; GSK3A^c	0.72	5	0.000849
Insulin/IGF pathway-protein kinase B signaling cascade	FOXB1; FOXB2; FOXD3; GSK3A^c	0.56	4	0.00252
Wnt signaling pathway	NKD2^c; GNG4; CCND1; GSK3A^c; CREBBP^c; AXIN1; LEF1	1.99	7	0.00405
Transcription regulation by bZIP transcription factor	MTERF; CREBBP^cTAF7	0.33	3	0.00471

^aExpected hits: expected number of hits by chance in the reference gene list; ^bP values of the binomial test between the BRAF mutation-specific gene list and the reference gene list; ^c targets with low tumor/normal log2 ratios in the BRAF wildtype group, suggesting that additional mechanisms, such as genomic loss, may play a role.

ISSN: 1868-7083