Somatic VHL Mutation in a Patient With MEN1-Associated Metastatic Pancreatic Neuroendocrine Tumor Responding to Sunitinib Treatment: A Case Report
| Autor: | Fatima Karzai, Apostolos Gaitanidis, Martha Quezado, Paul S. Meltzer, Vladimir Neychev, Jack Zhu, Keith Killian, Astin Powers, Patience Green, Jasmine Shell, Electron Kebebew, Dhaval Patel |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Oncology medicine.medical_specialty endocrine system diseases Somatic cell sunitinib Endocrinology Diabetes and Metabolism Nonsense mutation Case Reports urologic and male genital diseases Germline Loss of heterozygosity 03 medical and health sciences 0302 clinical medicine Germline mutation Internal medicine medicine multiple endocrine neoplasia MEN1 Multiple endocrine neoplasia Sunitinib business.industry Pituitary and Neuroendocrinology medicine.disease type 1 030104 developmental biology 030220 oncology & carcinogenesis von Hippel Lindau business medicine.drug |
| Zdroj: | Journal of the Endocrine Society |
| ISSN: | 2472-1972 |
| DOI: | 10.1210/js.2017-00156 |
| Popis: | Multiple endocrine neoplasia type 1 (MEN1) and von Hippel-Lindau (VHL) are autosomal-dominant diseases caused by germline mutations in tumor-suppressor genes. A patient with a germline MEN1 mutation and a somatic VHL mutation in the tumor has not been reported. Herein, we report on a patient with MEN1 and a metastatic nonfunctioning pancreatic neuroendocrine tumor (PNET) with a somatic VHL mutation. This patient underwent a pancreaticoduodenectomy for a grade 2 PNET obstructing her pancreatic duct. The patient developed liver and regional lymph node metastases as well as growth of a PNET in the remnant pancreas. As part of a clinical trial for mutation-targeted therapy, a biopsy of the metastatic tumor was obtained. The clinical diagnosis, confirmed by OncoVAR-NET and molecular profiling analysis, revealed MEN1 with a germline deletion in exon 2 and a c.402 deletion C, p.Phe134LeufsX51. In addition, a somatic mutation in the VHL gene—a nonsense mutation, c.529A>T, p.Arg177Ter—was identified by hybrid capture sequencing. The mutations were confirmed by Sanger sequencing. Comparative genomic hybridization showed loss of heterozygosity in both the MEN1 and VHL genes. The patient was treated with sunitinib and had a partial response to treatment. This case illustrates not only that a second hit occurs in tumor suppressor genes but that somatic mutations are also possible in additional tumor suppressor genes. This suggests that targeted therapy selection should include analysis of somatic mutations even when the susceptibility gene is known. The case report presents a rare finding in a patient with MEN1-associated metastatic PNET who had a somatic VHL mutation and responded to sunitinib treatment. The manuscript Somatic VHL mutation in a patient with MEN1-associated metastatic pancreatic neuroendocrine tumor responding to sunitinib treatment: A Case Report presents a rare finding in a patient with metastatic PNET. After operative resection, mutational analysis was conducted using tumor DNA. Loss of heterozygosity was noted in VHL and MEN1. |
| Databáze: | OpenAIRE |
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