Table 3.
Genes somatically targeted in pancreatic cancer.
| Gene | Chromosome | Gene type | Type of alteration | Percentage of cancers with alteration | Implications for pathologists/clinicians |
|---|---|---|---|---|---|
| KRAS | 12p | Onc | IM, rarely amplified | 95 | |
| CDKN2A | 9p | TSG | HD, LOH + IM, Meth | 95 | |
| TP53 | 17p | TSG | LOH + IM | 75 | |
| SMAD4 | 18q | TSG | HD, LOH + IM | 55 | IHC can be used to determine if a lesion is likely to be a metastasis from a pancreatic primary |
| ARID1A | 1p | TSG | IM + LOH | 3 | |
| RNF43 | 17q | TSG | IM + LOH | <10 | IPMN associated PDAC |
| GNAS | Onc | IM | <5 | IPMN associated PDAC | |
| TGFβR2 | 3p | TSG | IM + LOH, HD | <5 | |
| TGFβR1 | 9q | TSG | HD | <1 | |
| FBXW7 | 4q | TSG | LOH + IM | 3 | |
| MYC | 8p | Onc | Amp | 5–10 | Potentially therapeutically targetable |
| GATA6 | 18q | Onc | AMP | <5 | Tend to have a “classical” pattern of RNA expression. |
| ERBB2 | 17p | Onc | Amp + IM | 1 | Therapeutically targetable |
| BRAF | 7q | Onc | IM, deletion | <5 | Potentially therapeutically targetable |
| AKT2 | 19q | Onc | Amp | <5 | |
| ATM | 11q | TSG | IM + LOH | 1–5 | Potentially therapeutically targetable |
| BRCA2 | 13q | TSG | IM + LOH | 1–5 | Therapeutically targetable |
| MLH1 | 3p | MMR | IM LOH, Meth | 1 | Immune checkpoint inhibitors |
| NRG1 | Fusions | <5 | Therapeutic target of KRAS wild-type PDAC | ||
| KDM6A | X | TSG | IM + LOH | 3 | |
| STK11 | 19p | TSG | IM + LOH | 1 | |
| RB1 | 13q | TSG | IM + LOH | 1–2 | |
| ACVR1β | 12q | TSG | HD, LOH + IM | <1 | |
| ACVR2 | 2q | TSG | HD, LOH + IM | <1 | |
| ROBO2 | 3p | TSG | LOH | 1–2 | |
| PIK3CA | 3q | Onc | 1–3 | Potentially therapeutically targetable | |
| CCNE1 | 19p | Onc | Amp | <1 | |
| NTRK1 | 1q | Onc | Fusion | <1 | Potentially therapeutically targetable |
| CDK4 | 12q | Onc | Amp | <1 | Potentially therapeutically targetable |
| CDK6 | 7q | Onc | Amp | <1 | Potentially therapeutically targetable |
| FGFR1 | 8p | Onc | Amp | <1 | Potentially therapeutically targetable |
AMP amplification, HD homozygous deletion, IG intragenic, IHC immunohistochemical labeling, LOH loss of heterozygosity, Meth aberrant methylation, MMR DNA mismatch repair, Onc oncogene, Repair DNA repair gene, TSG tumor suppressor gene.