Molecular pathology of intraductal papillary mucinous neoplasms of the pancreas

Table 1 Most commonly oncogenes genetically altered in intraductal papillary mucinous neoplasms

Ref.	Gene symbol	Gene name	Mechanism of genetic alteration	Chromosome site	Known or predicted function	Alteration in IPMN
Z’graggen et al[24], 1997	KRAS2	v-Ki-ras-2 Kirsten	Point mutation	12p12.1	Signal transduction, proliferation, cell survival, motility	81.2%
		rat sarcoma
		viral oncogene
		homolog
Dal Molin et al[36], 2013	GNAS	GNAS complex locus	Point mutation	20q13.3	G-protein beta/gamma-subunit complex binding	61%
Schönleben et al[41], 2006	PI3KCA	Phosphoinositide-3-kinase	Point mutation	3q26.3	Proliferation, differentation, chemotaxis, survival, trafficking, glucose homeostasis	11%
Schönleben et al[22], 2007	BRAF	v-raf murine sarcoma viral oncogene homolog B1	Point mutation	7q34	Signal transduction, cell growth	2.7%
Hashimoto et al[48], 2008	TERT	Telomerase reverse transcriptase	Deletion,	5p15.3	Genome stability	70.6%
			nonsynonymous mutation, polymorphisms
Jang et al[50], 2007	SHH	Sonic hedgehog	Point mutation, missense mutation	7q36	Cell growth, cell specialization, proliferation of adult stem cells	61.8%

IPMN: Intraductal papillary mucinous neoplasms.

Table 2 Most commonly tumor suppressor genes genetically altered in intraductal papillary mucinous neoplasms

Ref.	Gene symbol	Gene name	Mechanism of genetic alteration	Chromosome site	Known or predicted function	Alteration in IPMN
Wada et al[26], 2002	CDKN2A/p16	Cyclin-dependent kinase inhibitor 2A	Homozygous deletion (41%), intragenic mutation (38%)	9p21	Cyclin-dependent kinase inhibitor	38.1%
Wada et al[26], 2002	TP53	Tumor protein p53	Intragenic mutation in 1 allele and loss in the other allele	17p13.1	Cell cycle arrest, apoptosis, senescence, DNA repair, metabolism change	27.3%
Biankin et al[55], 2002	SMAD4/DPC4	Mothers against decapentaplegic homolog of 4, drosophila	Homozygous deletion (50%), intragenic mutation in 1 allele and loss in the other allele (50%)	18q21.1	Signal transmission	16.7%
Sato et al[77], 2001	STK11/LKB1	Serine/threonine kinase 11	Homozygous deletion, intragenic mutation in 1 allele and loss in the other allele	19p13.3	Apoptosis regulation	32% (100% in patients with PJS and 25% in patients without PJS)
Dal Molin et al[81], 2012	BRG1	Brahma-related gene-1	Homozygous deletion, intragenic mutation in 1 allele and loss in the other allele	19p13.2	Regulation of cellular proliferation, regulation of several genes involved in key steps in tumorigenesis	53.3%

IPMN: Intraductal papillary mucinous neoplasm; PJS: Peutz-jeghers syndrome.

Table 3 Correlation between mutation of the gene and grade of dysplasia of intraductal papillary mucinous neoplasm

Ref.	Gene	Adenoma	Borderline	Carcinoma in situ	Invasive carcinoma
Wu et al[29], 2011	KRAS2	87%	90.2%	70.7%	70.7%
Dal Molin et al[36], 2013	GNAS	19%	23%	58%	58%
Schönleben et al[41], 2006	PI3KCA	0%	2.7%	2.7%	5.5%
Schönleben et al[22], 2007	BRAF	0%	0%	0%	2.7%
Hashimoto et al[48], 2008	hTERT	15.8%	35.7%	85%	86.7%
Jang et al[50], 2007	Shh	46.2%	35.7%	80%	84.6%
Wada[26], 2002	CDKN2A/p16	12.5%	20%	33%	100%
Abe et al[64], 2007; Wada et al[26], 2002	p53	0%	33.3%	38.5%	100%
Biankin et al[55], 2002	DPC4	0%	0%	38%	75%
Dal Molin et al[81], 2012	BRG1	28%	52%	76%	76%
Jang et al[23], 2009	S100A4	7.4%	7.4%	42.9%	42.9%

Table 4 Mucin expression profiles of the histological subtypes of intraductal papillary mucinous neoplasm

	MUC1	MUC2	MUC5AC	MUC6
Gastric	-	-	+	-
Intestinal	-	+	+	-
Pancreatobiliary	+	-	+	+
Oncocytic	-	-	+	+

MUC: Mucin.