Post-therapy emergence of an NBN reversion mutation in a patient with pancreatic acinar cell carcinoma

Post-therapy emergence of an NBN reversion mutation in a patient with pancreatic acinar cell carcinoma

Blog Article

Abstract Pancreatic acinar cell carcinoma (PACC) is a rare form of pancreatic cancer that commonly harbors targetable alterations, including activating fusions in the MAPK pathway and loss-of-function (LOF) alterations in DNA damage response/homologous recombination DNA repair-related genes.Here, we describe a patient with PACC harboring both somatic biallelic LOF of NBN and an activating NTRK1 fusion.Upon disease progression following 13 months Signs/Plaques of treatment with folinic acid, fluorouracil, irinotecan, and oxaliplatin (FOLFIRINOX), genomic analysis of a metastatic liver biopsy revealed the emergence of a novel reversion mutation restoring the reading frame of NBN.To our knowledge, genomic reversion 624 of NBN has not been previously reported as a resistance mechanism in any tumor type.The patient was treated with, but did not respond to, targeted treatment with a selective NTRK inhibitor.

This case highlights the complex but highly actionable genomic landscape of PACC and underlines the value of genomic profiling of rare tumor types such as PACC.