Neuregulin 1 fusion-positive cholangiocarcinoma

Neuregulin 1 (NRG1) fusion-positive cholangiocarcinoma is an exceedingly rare, biologically distinct molecular subtype of bile duct adenocarcinoma affecting the intrahepatic or extrahepatic biliary tract Clinically, these tumors behave aggressively, often presenting at an advanced or metastatic stage and frequently arising in younger adults compared with typical cholangiocarcinoma populations

Neuregulin 1 (NRG1) fusion-positive cholangiocarcinoma is an exceedingly rare, biologically distinct molecular subtype of bile duct adenocarcinoma affecting the intrahepatic or extrahepatic biliary tract The condition is characterized by chromosomal rearrangements that join the *NRG1* gene with various upstream fusion partners These chimeric transcripts generate aberrantly expressed chimeric NRG1 ligands that constitutively bind human epidermal growth factor receptor 3 (HER3), inducing dimerizat...

The condition is characterized by chromosomal rearrangements that join the *NRG1* gene with various upstream fusion partners

These chimeric transcripts generate aberrantly expressed chimeric NRG1 ligands that constitutively bind human epidermal growth factor receptor 3 (HER3), inducing dimerization with HER2 and triggering uncontrolled oncogenic signaling cascades, such as the MAPK and PI3K/Akt pathways

Clinically, these tumors behave aggressively, often presenting at an advanced or metastatic stage and frequently arising in younger adults compared with typical cholangiocarcinoma populations