Epigenetic landscape of gastrointestinal stromal tumors: Mechanistic insights and therapeutic opportunities

Table 2 Prognostic biomarkers of DNA methylation in gastrointestinal stromal tumors[32,41,73,75,79-82]

Ref.	Cohort/samples	Targets	Methodology	Key findings
Geddert et al[32]	200 GISTs	CD133 promoter	MSP + IHC	Hypermethylation associated with reduced CD133 expression; paradoxically, CD133 expression predicted shorter DFS
Haller et al[75]	150 GISTs	SPP1 (osteopontin)	Locus-specific assays	Hypomethylation predicted poor DFS across size, site, and mitotic index
House et al[79]	38 gastric GISTs	E-cadherin (CDH1)	MSP + protein	Methylation correlated with loss of E-cadherin and independently predicted recurrence/mortality
Ricci et al[80]	Gastric GISTs	p16INK4a promoter	MSP + IHC	Hypermethylation linked to protein loss and poor outcome
Lou et al[81]	115 cases	REC8, PAX3, p16	MCAM + validation	≥ 1 gene methylated correlated with poor survival; site-specific patterns identified
Niinuma et al[41]	91 cases	MEG3	Methylation + transcript	Hypermethylation correlated with poor prognosis; restoration activated interferon responses
Ohshima et al[73]	KIT exon 11 Δ557-558	Genome-wide	WGS + methylome	Hypomethylation signature linked to CNV burden and p53 pathway inactivation; aggressive behavior
Kleijn et al[82]	28 patients	Genome-wide	EPIC methylome + CNV	CNV burden and DMRs associated with progression; added to risk models

GIST: Gastrointestinal stromal tumors; CD: Cluster of differentiation; IHC: Immunohistochemistry; MSP: Methylation-specific polymerase chain reaction; DFS: Disease-free survival; CNV: Copy number variation; WGS: Whole-genome sequencing; DMR: Differentially methylated region; EPIC: Illumina EPIC methylation array.