Table 1.

Summary of reviewed genes that are related to epigenetic alterations during PDA progression and metastasis in the categories of germline PTV mutation, somatic mutation, chromatin accessibility and nucleosome remodeling, histone modification, and DNA methylation. ↓ denotes decrease and ↑ denotes increase.

Category	Gene	Molecular Function	Molecular Phenotype in PDA	Functional Phenotype in PDA	Reference
Germline PTV Mutation in Epigenetic Regulators	TET2	Dioxygenase of 5-methylcytosine, involved in demethylation of cytosines	loss of function in encoded protein	↓ patient survival	[12]
	DNMT3a	DNA methyltransferase, involved in de novo DNA methylation	loss of function in encoded protein	↓ patient survival	[12]
	ASXL1	Polycomb group protein, involved in gene transcriptional regulation and chromatin architecture maintenance	loss of function in encoded protein	↑ proliferation, ↓ patient survival	[12]
Somatic Mutation in Epigenetic Regulators	ARID1A	Chromatin remodeler, involved in chromatin remodeling and gene transcriptional regulation	loss of function in encoded protein	↑ progression, ↓ survival	[6,7,8,13,14]
	KDM6A	Lysine-specific histone demethylase, involved in promoter and enhancer activities	loss of function in encoded protein	↑ squamous identity, ↓ survival	[6,7,13,14]
Chromatin Accessibility	ZKSCAN1	Transcription factor, involved in proliferation and differentiation	↑ TF binding via open chromatin	↑ metastasis	[15]
	HNF1B	Transcription factor, involved in beta cell development in the pancreas	↓ TF binding via closed chromatin	↑ metastasis	[15]
Transcription Factor-Mediated Histone Modification	FOXA1	Transcription factor, involved in cell differentiation and chromatin remodeling	↑ enhancer activation (H3K27ac)	↑ cell growth, ↑ invasion, ↑ progression	[16]
	TP63	Transcription factor, involved in cell proliferation, differentiation, and apoptosis	↑ enhancer activation (H3K27ac)	↑ squamous identity	[17]
DNA Methylation	TFPI-2	Serine proteinase inhibitor, involved in negative regulation of pro-metastasis extracellular matrix degradation	↓ expression via hypermethylation	↑ progression, ↑ proliferation, ↑ migration	[18]
	RELN	Extracellular matrix serine protease, involved in neuronal migration	↓ expression via hypermethylation	↓ patient survival, ↑ migration, ↑ invasion, ↑ colony formation	[19]
	MET	Receptor tyrosine kinase, involved in cell survival, migration, and invasion	↑ expression via hypomethylation	↓ patient survival	[20]
	ITGA2	Integrin, involved in adhesion of cells to the extracellular matrix	↑ expression via hypomethylation	↓ patient survival	[20]