Document Type
Journal Article
Study Type
Case Report
Publication Date
9-1-2017
Journal
Journal of the Endocrine Society
Volume
1
Issue
9
Inclusive Pages
1124–1134
DOI
10.1210/js.2017-00156
Abstract
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.
Creative Commons License
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License.
APA Citation
Shell, J., Patel, D., Powers, A., Quezado, M., Killian, K., Meltzer, P., Zhu, J., Gaitanidis, A., Karzai, F., Neychev, V., Green, P., & Kebebew, E. (2017). Somatic VHL Mutation in a Patient With MEN1-Associated Metastatic Pancreatic Neuroendocrine Tumor Responding to Sunitinib Treatment: A Case Report.. Journal of the Endocrine Society, 1 (9). http://dx.doi.org/10.1210/js.2017-00156
Peer Reviewed
1
Open Access
1
Comments
Reproduced with permission of Oxford University Press. Journal of the Endocrine Society.