Table 2.

Frequency and consequences of common genetic mutations in pancreatic ductal adenocarcinoma

Mutation category	Frequency in PDAC	Effects of mutation	Consequence
Gain of function
KRAS	> 95%	Continuous transduction of downstream growth signals (BRAF/MAPK, PI3K/mTOR)	Enhanced cell growth and survival
Loss of function
CDKN2A	95%	Disruption of RB1 by CDK4	Uncontrolled cellular proliferation
TP53	75%-85%	Impaired DNA damage repair, loss of cell cycle checkpoint activation	Chromosomal instability, aneuploidy
DPC4/SMAD4	50%	Loss of inhibition of TGF-β	Loss of cell growth inhibition
BRCA2	6%-17%	Impaired DNA damage repair by homologous recombination, loss of cell-cycle checkpoint activation	Genomic instability
PALB2	1%-3%	Impaired BRCA2 function	Genomic instability

KRAS: Kirsten rat sarcoma oncogene; BRAF: Rapidly activated fibrosarcoma homolog B; MAPK: Mitogen activated protein kinase; PI3K: Phosphatidyl inositol-3 kinase; mTOR: Mammalian target of rapamycin; CDK: Cyclin dependent kinase; DPC4: Deleted in pancreatic cancer 4; TGF-β: Transforming growth factor-β; BRCA2: Breast cancer 2; PALB2: Partner and localizer of BRCA.