Table 2 Top differentially methylated signaling pathway genes distinguishing intra- from extracranial metastases.

From: Patient-specific identification of genome-wide DNA-methylation differences between intracranial and extracranial melanoma metastases

Gene	Methylation state in intracranial metastases	Number of patients	Affected region	Affected CpG identifiers	Biological process	Role in cancer/other diseases	References
TNXB	Decreased	10	Body	cg00525277, cg00872984, cg01337207, cg01569346, cg01992382, cg07524919, cg10365886, cg10890302, cg16834823, cg17662683, cg26266427, cg27387193	Cell adhesion	Ehlers-Danlos syndrome	⁴⁴
PRKCA	Decreased	9	Body	cg01895374, cg12467435, cg14766208	Cell signaling	Glioma	⁴⁵* ,⁴⁶*
BMP4	Increased	9	Body	cg16389901	Cell growth	Gastric cancer	⁴⁷*
DUSP6	Decreased	9	Body	cg00772407, cg07239716	Cell growth	Pancreatic, gastric cancer	⁴⁸,⁴⁹
SGK1	Decreased	9	Body	cg08550353	Cell death	Epilepsy, schizophrenia, Alzheimers disease, Colon cancer, gastric cancer	^50,51, ⁵², ⁵³
ITGB7	Decreased	9	Promoter	cg11510999, cg18320160	Cell adhesion	Breast cancer	⁵⁴*
EIF4B	Decreased	9	Body	cg21613259, cg24828692	Translation regulation	Alzheimers disease	⁵⁵
G6PC3	Decreased	9	Promoter	cg18426551, cg22243039, cg26534477	Metabolism	Neutropenia	^56,57
CACNA2D3	Decreased	8	Body	cg01951202, cg06372503, cg10313834, cg24875570	Cell signaling (Ca2+)	Breast cancer metastases	⁵⁸*
CACNG8	Decreased	8	Body	cg26548871	Cell signaling (Ca2+)	Schizophrenia	⁵⁹
RASGRF1	Decreased	8	Body	cg02587988	Cell signaling	Colorectal cancer	⁶⁰*
GDF15	Decreased	8	Body	cg03207391	Cell growth	Colorectal cancer	⁶¹*
IGF1R	Decreased	8	Body, enhancer, Promoter	cg03380198, cg19322380, cg25404375, cg27139419	Cell growth
MECOM	Increased	8	Body	cg00988247, cg01277372	Cell death	Leukemia	⁶²*
TNR	Decreased	8	Body	cg09319617	Cell adhesion	Parkinsons disease	⁶³
JAK3	Decreased	8	Body	cg05796838	Immune response	Leukemia	⁶⁴*
LRTM1	Decreased	8	Body	cg24875570	Transmembran domain

The table represents in-depth information about the 17 signaling pathway genes that contained at least one CpG whose methylation level was altered in the same direction in at least 8 of 14 patients. The observed methylation change in intracranial metastases is reported in the column ‘Methylation state in intracranial metastases’ along with the number of patients whose metastases pair showed the same behavior provided in the column ‘Number of patients’. The affected region of a gene is provided in the column ‘Affected region’, affected CpGs are listed in the column ’Affected CpG identifiers’, and corresponding gene functions from GeneCards⁶⁵ and Uniprot⁶⁶ are summarized in the column ’Biological process’. Results of an in-depth literature analysis in relation to cancer and other diseases are summarized in the column ‘Role in cancer / other diseases’. Relevant references are listed in the column ’References’. References that indicate associations of a specific gene in relation to cancer are marked with an asterisk ‘*’.

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Table 2 Top differentially methylated signaling pathway genes distinguishing intra- from extracranial metastases.

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