Epigenetics and pancreatic cancer: Pathophysiology and novel treatment aspects

Table 2 Activated and deactivated key genes in pancreatic cancer according to hallmark of cancer, frequency as well as to kind of possible genetic and epigenetic alteration

Gene symbol (source)	Associated function according the hallmarks of cancer1[35,36]	Frequency	Type of genetic alteration	Evidence for epigenetic regulation (reference)
Activation
K-RAS2[131]	a, f, g	> 90	Point mutation
AKT2[162,163]	a, j, g	10-20	Amplification
BRAF[164]	a, b, g	5	Point mutation
Deactivation
CDKN2A/p16[165]	b, d, i	95	Homozygous deletion, intragenic mutation	Yes[166]
TP53[167-169]	b, d, i, h	50-70	Intragenic mutation an one allele and loss in the other allele
SMAD4/DPC4[170,171]	b, c, f	55	Homozygous deletion, intragenic mutation
MLH1[23,172]	h	3-15	Heterozygote mutations	Yes[34]
BRCA2[173]	a	7	Heterozygote mutations
STK11/LKB1[174]	i	5	Homozygous deletion, intragenic mutation
TGFBR2[175]	a, f	4	Homozygous deletion, homozygous frameshift mutation
MAP2K4[176,177]	a	2	Homozygous deletion, missense mutation

¹Hallmarks of cancer: Sustaining proliferative signaling (a), evading growth suppressors (b), avoiding immune destruction (c), enabling replicative immortality (d), tumour promoting inflammation (e), activating invasion and metastasis (f), inducing angiogenesis (g), genome instability and mutations (h), resisting cell death (i), deregulating cellular energetics (j)[35,36].