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Table 2 Sporadic and inherited genetic alterations in pancreatic ductal adenocarcinoma

From: Pancreatic cancer genomics: insights and opportunities for clinical translation

Genes Full name Known function(s) Location Effect‡ Prevalence S/I§ Other cancers Inherited syndrome Est. rel. risk (if known) References
None       - None None 1  
KRAS v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog GDP/GTP binding proteins, proliferation, survival, others 12p12.1 Act 90-95% S Bladder, breast, leukemia, and lung Cardiofaciocutaneous syndrome   [15, 16, 96]
CDKN2A (p16) Cyclin-dependent kinase inhibitor 2A Cell cycle 9p21.3 In 90% S/I Melanoma FAMMM 20-34X [97, 98]
TP53 Tumor protein p53 Cell cycle, apoptosis, DNA repair, others 17p13.1 In 75% S Breast, colorectal, hepatocellular, others Li-Fraumeni syndrome   [99]
SMAD4/DPC4 SMAD family member 4 TGF-β signaling, BMP signaling, development, proliferation, others 18q21.2 In 55% S Colorectal Juvenile polyposis syndrome, Myhre syndrome   [2628, 100, 101]
TGFBR1,2 Transforming growth factor, beta receptor 1, 2 TGF-β signaling, development, proliferation, others 9q22.33, 3p24.1 In 5-10% S Colorectal, esophageal Loeys-Dietz syndrome   [29, 102]
ACVR1B Activin A receptor, type IB TGF-β signaling, development, proliferation, others 12q13.13 In 5-10% S Unknown Unknown   [30]
MKK4 Mitogen-activated protein kinase kinase 4 Cell stress, JNK signaling 17p12 In 5-10% S Unknown Unknown   [103]
MLL3 Myeloid/lymphoid or mixed-lineage leukemia 3 Chromatin remodeling, transcription 7q36.1 In <10% S Breast, colorectal, and leukemia    [16, 104]
ARID1A/B AT-rich interaction domain-containing protein 1A/B Chromatin remodeling, transcription 1p36.11, 6q25.3 In <10% S Breast, ovary and liver Coffin-Siris syndrome   [16, 105, 106]
PBRM1 Polybromo 1 Chromatin remodeling, transcription 3p21.1 In <10% S Kidney    [16, 106]
SMARCA4 Swi/Snf-related, matrix associated, actin-dependent regulator of chromatin, subfamily A, member 4 Chromatin remodeling, transcription 19p13.2 In <10% S Lung Coffin-Siris syndrome, rhaboid tumor predisposition syndrome   [16, 105107]
BRCA1, BRCA2 Breast cancer 1, early onset, breast cancer 2, early onset DNA repair, cell cycle, genome stability 17q21.31, 13q13.1 In <10% I Breast, ovary and prostate Breast cancer 3.5-10X, 2X [34, 108, 109]
PALB2, ATM, others Partner and localizer of BRCA2, Ataxia telangiectasia mutated DNA repair, cell cycle, genome stability 7q34 In <10% I Unknown Familial pancreatic cancer¥ 32X (overall) [31, 32, 35, 39, 40]
PRSS1 Protease, serine, 1 (trypsin 1) Cell metabolism and signaling 19p13.3 In <10% I None Familial pancreatitis 50-80X [110]
STK11/LKB1 Serine/threonine kinase 11 p53 signaling, DNA repair, apoptosis 3p22.2, 2p21 In <10% I Breast, colorectal, gastroesophageal, and small bowel Peutz-Jeghers syndrome 132X [33, 111]
hMLH1, hMSH2, others MutL Homolog 1, colon cancer, nonpolyposis type 2 (I), mutS homolog 2, colon cancer, nonpolyposis type 1 (I) DNA mismatch repair 9q22.32, 9p13.3 In <10% I Biliary tract, brain, colorectal, endometrial, ovarian, stomach, ureter and renal pelvis HNPCC   [112, 113]
FANC-C, FANC-G Fanconi anemia, complementation group C, Fanconi anemia, complementation group G DNA stability and repair 9q22, 9p13 In <10% I Unknown Young-age-onset pancreatic cancer   [3638]
  1. Effect of mutation: Act, activating; In, inactivating. §Commonly sporadic (S) or inherited (I). This relative risk applies only to patients with germline CDKN2A mutations. ¥Familial pancreatic cancer is defined by three first degree relatives in these studies.