Molecular alterations in pancreatic tumors

Table 1 Main genetic alterations detectable in pancreatic ductal adenocarcinoma

Type of pancreatic lesion	Genetic alteration	Reported frequency (%)	Type of alterations	Role in clinical practice
PDAC	KRAS	70-90	Point mutations	Diagnostic/prognostic
	TP53	50-75	Point mutations/LOH	Prognostic
	CDKN2A/p16	90-98	Point mutations/LOH	Prognostic/genetic surveillance
	SMAD4	40-60	Point mutations/LOH	Prognostic
	BRCA1/2	5-10	Point mutations	Predictive/genetic surveillance
	NTRK1-3	< 1	Gene fusions	Predictive
	MSI	< 2	LOF	Predictive

The percentages quoted are estimated from the literature cited in the paper. Diagnostic role appears mainly in preoperative material. In bold those markers recommended for clinical practice by National Comprehensive Cancer Network 2019 guidelines. PDAC: Pancreatic ductal adenocarcinoma; LOH: Loss of heterozygosity.

Table 2 Main genetic alterations detectable in cystic pancreatic lesions

Type of pancreatic lesion	Genetic alteration	Reported frequency (%)	Type of alterations	Role in clinical practice
IPMN	KRAS	90	Point mutations	Diagnostic
	TP53	10	Point mutations/LOH	Prognostic
	GNAS	40-60	Point mutations	Diagnostic
	RNF43	25	Point mutations/LOH	Diagnostic
MCN	KRAS	0-25% (LG); 50-90% (HG)	Point mutations	Diagnostic
	CDKN2A/p16	0-10 (LG); 50 (HG)	Point mutations/LOH	Prognostic
	TP53	0 (LG); 20-50 (HG)	Point mutations/LOH	Prognostic
SCN	VHL	40-60	Point mutations/LOH	Diagnostic

The percentages quoted are estimated from the literature cited in the paper. Diagnostic role appears mainly in preoperative material. IPMN: Intraductal papillary mucinous neoplasms; MCN: Mucinous cystic neoplasia; LG: Low-grade mucinous cystic neoplasia; HG: High-grade mucinous cystic neoplasia; SCN: Serous cystic neoplasm; LOH: Loss of heterozygosity.

Table 3 Main genetic alterations detectable in other pancreatic tumors

Type of pancreatic lesion	Genetic alteration	Reported frequency (%)	Type of alterations	Role in clinical practice
SPN	CTNNB1	90-100	Point mutations	Diagnostic
PanNET	MEN1	70	Point mutations/LOH	Diagnostic/prognostic
	VHL	25	Point mutations/LOH	Diagnostic
AAC	CTNNB1	5-25	Point mutationsLOF	Diagnostic
	MSI	5-15	LOF	Predictive?

The percentages quoted are estimated from the literature cited in the paper. Diagnostic role appears mainly in preoperative material. SPN: Solid pseudopapillary neoplasm; PanNET: Pancreatic neuroendocrine tumor; AAC: Acinic adenocarcinoma; LOH: Loss of heterozygosity; LOF: Loss of function.