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

   


Authors: Pelster, M. S.; Silverman, I. M.; Schonhoft, J. D.; Johnson, A.; Selenica, P.; Ulanet, D.; Rimkunas, V.; Reis-Filho, J. S.
Article Title: Post-therapy emergence of an NBN reversion mutation in a patient with pancreatic acinar cell carcinoma
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 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. © The Author(s) 2024.
Keywords: clinical article; human tissue; treatment response; aged; cancer surgery; unclassified drug; human cell; sequence analysis; single nucleotide polymorphism; somatic mutation; frameshift mutation; case report; fluorouracil; cancer combination chemotherapy; drug withdrawal; treatment duration; capecitabine; gemcitabine; paclitaxel; cancer patient; pancreaticoduodenectomy; allele; gene expression profiling; tumor volume; ca 19-9 antigen; patient monitoring; mutational analysis; retrospective study; wild type; nibrin; irinotecan; drug dose escalation; genome analysis; liver metastasis; gene rearrangement; tumor burden; folinic acid; adjuvant chemotherapy; nucleotide sequence; protein mcl 1; gene fusion; dna damage response; chromosome translocation; heterozygosity loss; carcinomatous peritonitis; oxaliplatin; chromosome deletion; liver biopsy; genetic code; disease exacerbation; dna determination; genomic dna; chemoradiotherapy; nucleotide; phase 2 clinical trial (topic); phase 1 clinical trial (topic); smad4 protein; multicenter study (topic); indel mutation; multiplex polymerase chain reaction; chromosome inversion; chromosome duplication; nonsense mediated mrna decay; ploidy; high throughput sequencing; drug shortage; acinar cell carcinoma of the pancreas; dna sequencing; human; male; article; whole genome sequencing; rna sequencing; revertant; monoclonal antibody therapy; deletion mutation; larotrectinib; talazoparib; tumor mutational burden; locus of control; reading frame; oncogene fusion protein; camonsertib; osemitamab; sel1l ntrk1 fusion protein
Journal Title: npj Precision Oncology
Volume: 8
ISSN: 2397-768X
Publisher: Springer Nature  
Date Published: 2024-04-01
Start Page: 82
Language: English
DOI: 10.1038/s41698-024-00497-x
PROVIDER: scopus
PMCID: PMC10985087
PUBMED: 38561473
DOI/URL:

https://www.scopus.com/inward/record.uri?eid=2-s2.0-85189170031&doi=10.1038%2fs41698-024-00497-x&partnerID=40&md5=1abfb3e7fb89f3fbd11a670c7c183c9c
Notes: Article -- MSK Cancer Center Support Grant (P30 CA008748) acknowledged in PubMed and PDF -- Source: Scopus
Altmetric
What is Altmetric?
Citation Impact
What is Dimensions Citation Badge?
BMJ Impact Analytics
MSK Authors
  1. Jorge Sergio Reis-Filho
    639 Reis-Filho
  2. Pier Selenica
    190 Selenica
Related MSK Work