Table 2.
Non-canonical genetic and molecular alterations in pancreatic cancer variants.
| Subtype | Gene | Chromosome | Mutations | Encoded Protein | Functional Effects on Molecular Pathway |
|---|---|---|---|---|---|
| CC | GNAS | 20 | Somatic | Gα subunit of heterotrimeric G-proteins | GPCR-mediated signaling constitutively active |
| ATM | 11 | Germline | Serine/threonine kinase | DNA double strand break not tagged | |
| MLH1, MLH2, PMS2, MSH6 | 3, 2, 7, 2 | Germline | Protein-protein interactions in MMR | MSI | |
| Medullary carcinoma | MLH1, MLH2, PMS2, MSH6 | 3, 2, 7, 2 | Germline | Protein-protein interactions in MMR | MSI |
| POLE | 12 | Somatic | Catalytic subunit of the DNA polymerase | DNA damage | |
| ASC | UPF1 | 19 | Somatic | RNA helicase | Altered NMD |
| KMT2C, KMT2D, SMARCA4, KDM6, KDM3 | 7, 12, 19, X, 2 | n.a. | Chromatin modifiers | Altered chromatin architecture | |
| UDC | CDH1 | 16 | n.a. | E-cadherin, cell adhesion molecule | EMT |
| UCOGC | SERPINA3 | 14 | Somatic | α−1antichymotrypsin | n.a. |
| MAGEB4 | X | Somatic | Cancer antigen | n.a. | |
| GLI3 | 7 | Somatic | Transcription factor | Constitutive activation of HH signaling | |
| MEGF8 | 19 | Somatic | n.a. | Constitutive activation of HH signaling | |
| TTN | 2 | Somatic | Muscle assembly and functioning | n.a. | |
| BRCA2 | 13 | Somatic | Rad51 binding protein | DNA damage | |
| Rhabdoid carcinoma | SMARCB1 | 22 | Somatic | INI1 | Chromatin remodeling (BAF complex) |
| Hepatoid carcinoma | BAP1 | 3 | Somatic or germline | Ubiquitin carboxyl-terminal hydrolase | DNA damage |
| Notch1 | 9 | n.a. | Membrane receptor | Alteration in cell to cell interactions | |
| SRCC | n.a. | n.a. | n.a. | n.a. | PI3K and MEK1 constitutively active |
ASC, adenosquamous carcinoma; ATM, ataxia telangiectaisa mutated; BAP1, breast cancer gene 1 (BRCA1) associated protein 1; BRCA2, breast cancer 2; CC, colloid carcinoma; GPCR, G protein-coupled receptor; EMT, epithelial-to-mesenchymal transition; GLI3, glioma-associated oncogene 3; HH, hedgehog; KDM, lysine demethylase; KMT2, histone-lysine N-methyltransferase 2; MAGEB4, melanoma-associated antigen B4; MEGF8, multiple epidermal growth factor-like domains protein 8; MEK1, mitogen-activated protein kinase kinase 1; MMR, mismatch repair; MSI, microsatellite instability; n.a., not assessed; NMD, nonsense-mediated mRNA decay; PI3K, phosphoinositide 3-kinase; POLE, polymerase epsilon; SERPINA3, serpin peptidase inhibitor clade A member 3; SMARCB1, switch/sucrose non-fermentable (SWI/SNF) related, matrix associated, actin dependent regulator of chromatin, subfamily B, 1; SRCC, signet-ring cell carcinoma; UCOGC, undifferentiated carcinoma with osteoclast-like giant cells; UDC, undifferentiated carcinoma; UPF1, up-frameshift 1.