TY - JOUR
T1 - Somatic VHL mutation in a patient with MEN1-associated metastatic pancreatic neuroendocrine tumor responding to sunitinib treatment
T2 - A case report
AU - Shell, Jasmine
AU - Patel, Dhaval
AU - Powers, Astin
AU - Quezado, Martha
AU - Killian, Keith
AU - Meltzer, Paul
AU - Zhu, Jack
AU - Gaitanidis, Apostolos
AU - Karzai, Fatima
AU - Neychev, Vladimir
AU - Green, Patience
AU - Kebebew, Electron
N1 - Publisher Copyright:
© 2017 Endocrine Society.
PY - 2017/9
Y1 - 2017/9
N2 - 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 theMEN1 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.
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 theMEN1 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.
KW - Multiple endocrine neoplasia
KW - Sunitinib
KW - Type 1
KW - Von Hippel Lindau
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U2 - 10.1210/js.2017-00156
DO - 10.1210/js.2017-00156
M3 - Article
AN - SCOPUS:85052576825
SN - 2472-1972
VL - 1
SP - 1124
EP - 1134
JO - Journal of the Endocrine Society
JF - Journal of the Endocrine Society
IS - 9
ER -