Pancreatic Acinar Cell Carcinoma in the Setting of a BRCA1 Germline Mutation

Campoverde, Leticia; Vyas, Monika; Bullock, Andrea J.

doi:10.7326/aimcc.2022.0596

Cited by 1 publication

(1 citation statement)

References 15 publications

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“…Genomically, PACCs have a repertoire of alterations distinct from that of pancreatic ductal carcinomas, rarely displaying KRAS , TP53, CDKN2A , and SMAD4 somatic alterations, and more frequently harboring recurrent activating fusions affecting BRAF, RET , RAF1 , and NTRK1/2/3 , which are present in up to 30% of patients 2 – 7 . In addition, a subset of patients with PACCs harbor germline pathogenic alterations affecting DNA damage response (DDR)/homologous recombination (HR) DNA repair-related genes, including ATM , BRCA1 , BRCA2 , and PALB2 2 , 3 , 8 .…”

Section: Introductionmentioning

confidence: 99%

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

Pelster,

Silverman,

Schonhoft

et al. 2024

npj Precis. Onc.

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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 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 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.

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