GRCh38 · COSMIC v94

Summary

This section shows a summary for the selected study (COSU identifier) or publication (COSP identifier). Studies may have been performed by the Sanger Institute Cancer Genome Project, or imported from the ICGC/TCGA. You can see more information on the help pages.

Reference
Successful BRAF/MEK inhibition in a patient with BRAFV600E-mutated extrapancreatic acinar cell carcinoma.
Paper ID
COSP48541
Authors
Busch E, Kreutzfeldt S, Agaimy A, Mechtersheimer G, Horak P, Brors B, Hutter B, Fröhlich M, Uhrig S, Mayer P, Schröck E, Stenzinger A, Glimm H, Jäger D, Springfeld C, Fröhling S and Zschäbitz S
Affiliation
Department of Medical Oncology, University Hospital Heidelberg, National Center for Tumor Diseases (NCT) Heidelberg, Heidelberg, 69120, Germany.
Journal
Cold Spring Harbor molecular case studies, 2020;6(4)
ISSN: 2373-2873
PMID: 32843432 (view at PubMed or Europe PMC)
Abstract
Pancreatic acinar cell carcinoma (PAC) is a rare disease with a poor prognosis. Treatment options for metastatic PAC are limited and often follow chemotherapeutic regimens for pancreatic ductal adenocarcinoma. Although recurrent genomic alterations, such as <i>BRAF</i> fusions and defects in genes involved in homologous recombination DNA repair, have been described in PAC, data on the clinical efficacy of molecularly guided, targeted treatment are scarce. Here we describe the case of a 27-yr-old patient with <i>BRAF</i><sup>V600E</sup>-mutated PAC who was successfully treated with a combination of BRAF and MEK inhibitors. The patient presented to our clinic with abdominal pain and weight loss. Imaging showed extensive retroperitoneal disease as well as mediastinal lymphadenopathy. Because of elevated α-fetoprotein (AFP) levels and inconclusive histologic findings, a germ cell tumor was suspected; however, PEI chemotherapy was unsuccessful. A repeat biopsy yielded the diagnosis of PAC and treatment with FOLFIRINOX was initiated. Comprehensive molecular profiling within the MASTER (Molecularly Aided Stratification for Tumor Eradication Research) precision oncology program revealed a somatic <i>BRAF</i><sup>V600E</sup> mutation and a germline <i>PALB2</i> stop-gain mutation. Therapy was therefore switched to BRAF/MEK inhibition, resulting in almost complete remission and disease control for 12 mo and a remarkable improvement in the patient's general condition. These results indicate that <i>BRAF</i> alterations are a valid therapeutic target in PAC that should be routinely assessed in this patient population.
Paper Status
Curated