PMID- 29264567
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20201001
IS  - 2472-1972 (Print)
IS  - 2472-1972 (Electronic)
IS  - 2472-1972 (Linking)
VI  - 1
IP  - 9
DP  - 2017 Sep 1
TI  - Somatic VHL Mutation in a Patient With MEN1-Associated Metastatic Pancreatic 
      Neuroendocrine Tumor Responding to Sunitinib Treatment: A Case Report.
PG  - 1124-1134
LID - 10.1210/js.2017-00156 [doi]
AB  - 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.
FAU - Shell, Jasmine
AU  - Shell J
AD  - Endocrine Oncology Branch, National Cancer Institute, National Institutes of 
      Health, Bethesda, Maryland 20892.
FAU - Patel, Dhaval
AU  - Patel D
AD  - Endocrine Oncology Branch, National Cancer Institute, National Institutes of 
      Health, Bethesda, Maryland 20892.
FAU - Powers, Astin
AU  - Powers A
AD  - Laboratory of Pathology, National Cancer Institute, National Institutes of 
      Health, Bethesda, Maryland 20892.
FAU - Quezado, Martha
AU  - Quezado M
AD  - Laboratory of Pathology, National Cancer Institute, National Institutes of 
      Health, Bethesda, Maryland 20892.
FAU - Killian, Keith
AU  - Killian K
AD  - Genetics Branch, Center for Cancer Research, National Cancer Institute, National 
      Institutes of Health, Bethesda, Maryland 20892.
FAU - Meltzer, Paul
AU  - Meltzer P
AD  - Genetics Branch, Center for Cancer Research, National Cancer Institute, National 
      Institutes of Health, Bethesda, Maryland 20892.
FAU - Zhu, Jack
AU  - Zhu J
AD  - Genetics Branch, Center for Cancer Research, National Cancer Institute, National 
      Institutes of Health, Bethesda, Maryland 20892.
FAU - Gaitanidis, Apostolos
AU  - Gaitanidis A
AD  - Endocrine Oncology Branch, National Cancer Institute, National Institutes of 
      Health, Bethesda, Maryland 20892.
FAU - Karzai, Fatima
AU  - Karzai F
AD  - Genitourinary Malignancies Branch, Medical Oncology Service, National Cancer 
      Institute, National Institutes of Health, Bethesda, Maryland 20892.
FAU - Neychev, Vladimir
AU  - Neychev V
AD  - Endocrine Oncology Branch, National Cancer Institute, National Institutes of 
      Health, Bethesda, Maryland 20892.
FAU - Green, Patience
AU  - Green P
AD  - Endocrine Oncology Branch, National Cancer Institute, National Institutes of 
      Health, Bethesda, Maryland 20892.
FAU - Kebebew, Electron
AU  - Kebebew E
AD  - Endocrine Oncology Branch, National Cancer Institute, National Institutes of 
      Health, Bethesda, Maryland 20892.
AD  - Department of Surgery, The George Washington University School of Medicine and 
      Health Sciences, Washington, DC 20052.
LA  - eng
PT  - Case Reports
DEP - 20170707
PL  - United States
TA  - J Endocr Soc
JT  - Journal of the Endocrine Society
JID - 101697997
PMC - PMC5686673
OTO - NOTNLM
OT  - multiple endocrine neoplasia
OT  - sunitinib
OT  - type 1
OT  - von Hippel Lindau
EDAT- 2017/12/22 06:00
MHDA- 2017/12/22 06:01
PMCR- 2017/07/07
CRDT- 2017/12/22 06:00
PHST- 2017/03/23 00:00 [received]
PHST- 2017/06/27 00:00 [accepted]
PHST- 2017/12/22 06:00 [entrez]
PHST- 2017/12/22 06:00 [pubmed]
PHST- 2017/12/22 06:01 [medline]
PHST- 2017/07/07 00:00 [pmc-release]
AID - JS_201700156 [pii]
AID - 10.1210/js.2017-00156 [doi]
PST - epublish
SO  - J Endocr Soc. 2017 Jul 7;1(9):1124-1134. doi: 10.1210/js.2017-00156. eCollection 
      2017 Sep 1.