Table 4.
Genetic Alterations in Common Neoplasms of the Pancreas
| Tumor type | Gene(s) | Prevalence of the Alteration |
Comment |
|---|---|---|---|
| Acinar cell carcinoma | APC | 15% | |
| CTNNB1 (beta-catenin) | 5% | ||
| Invasive ductal adenocarcinoma | KRAS | 95% | |
| p16/CDKN2A | 95% | ||
| TP53 | 75% | ||
| SMAD4 | 55% | SMAD4 loss associated with poor prognosis and widespread disease | |
| MLL3, TGFBR2, FBXW7, ARID1A,AIRID2, and ATM | <5% | Some of these, such as ATM, may be targetable therapeutically | |
| IPMN | KRAS | 80% | |
| RNF43 | 75% | RNF43 is a marker of mucin-producing tumors as it is present in both IPMNs and MCNs | |
| GNAS | 60% | GNAS is a marker of IPMNs. GNAS and/or KRAS mutations are present in >95% of all IPMNs | |
| p16/CDKN2A | Varies dependent on histologic grade | ||
| TP53 | Varies dependent on histologic grade | Associated with higher grade lesions | |
| SMAD4 | Varies dependent on histologic grade | Associated with higher grade lesions | |
| PIK3CA | 10% | ||
| MCN | KRAS | 75% | |
| RNF43 | 40% | RNF43 is a marker of mucin-producing tumors--IPMNs and MCNs | |
| p16/CDKN2A | Varies dependent on histologic grade | ||
| TP53 | Varies dependent on histologic grade | Associated with higher grade lesions | |
| SMAD4 | Varies dependent on histologic grade | Associated with higher grade lesions | |
| Pancreatoblastoma | Imprinted region on chromosome 11 | 85% | Same region is targeted in hepatoblastoma and Wilms tumors |
| CTNNB1 (beta-catenin) | 55% | ||
| APC | 10% | ||
| PanNET | MEN1 | 45% | |
| DAXX or ATRX | 45% | ||
| TSC2, PTEN, DDIT4, and PIK3CA (mTOR Pathway genes) | 15% | Potentially targetable therapeutically with everolimus | |
| SCN | VHL | 50% | Among the cystic tumors of the pancreas, VHL loss is specific for SCN |
| SPN | CTNNB1 (beta-catenin) | 95% | Immunolabeling for beta-catenin is useful diagnostically |
IPMN=intraductal papillary mucinous neoplasm; MCN=mucinous cystic neoplasm; PanNET=pancreatic neuroendocrine tumor; SCN=serous cystic neoplasm; SPN=solid-pseudopapillary neoplasm