PMID- 25733923
OWN - NLM
STAT- PubMed-not-MEDLINE
DCOM- 20150303
LR  - 20201001
IS  - 1178-704X (Print)
IS  - 1178-704X (Electronic)
IS  - 1178-704X (Linking)
VI  - 8
DP  - 2015
TI  - Bilateral granulosa cell tumors: a novel malignant manifestation of multiple 
      endocrine neoplasia 1 syndrome found in a patient with a rare menin in-frame 
      deletion.
PG  - 69-73
LID - 10.2147/TACG.S72223 [doi]
AB  - INTRODUCTION: Multiple endocrine neoplasia 1 (MEN1) is a cancer syndrome 
      resulting from mutations of the MEN1 gene. The syndrome is characterized by 
      neoplasia of the parathyroid and pituitary glands, and malignant tumors of the 
      endocrine pancreas. Other manifestations include benign lipomas, angiofibromas, 
      and carcinoid tumors commonly originating in the colon, thymus, and lung. This is 
      the first report of MEN1 syndrome manifesting as bilateral granulosa cell ovarian 
      tumors, and which is associated with a rare intronic mutation of the MEN1 gene. 
      CASE REPORT: A 41-year-old woman presented with abdominal pain, increasing 
      abdominal girth, and dysmenorrhea. Ultrasound demonstrated enlarged ovaries and 
      uterine fibroids. After an exploratory laparotomy, she subsequently underwent 
      bilateral salpingo-oophorectomy with hysterectomy where the pathology revealed 
      bilateral cystic granulosa cell tumors of the ovaries. Additional workup 
      including computed tomography imaging discovered a thymic mass, which the 
      pathology showed was malignant, along with a pancreatic mass suspicious for a 
      neuroendocrine tumor. Hyperparathyroidism was also discovered and was found to be 
      secondary to a parathyroid adenoma. Genetic testing revealed an exceedingly rare 
      mutation in the MEN1 gene (c.654 + 1 G>A). DISCUSSION: Mutations of the menin 
      gene leading to MEN1 syndrome are classically nonsense or missense mutations 
      producing a dysfunctional protein product. Recently, researchers described a 
      novel mutation of MEN1 (c.654 + 1 G>A) in a male proband meeting the criteria for 
      clinical MEN1 syndrome. Functional analysis performed on the stable mutant 
      protein showed selective disruption of the transforming growth factor beta 
      signaling pathway, yet it maintained its wild-type ability to inhibit nuclear 
      factor kappa B and to suppress JunD transcriptional activity. CONCLUSION: To our 
      knowledge, this is the first report of MEN1 syndrome associated with bilateral 
      granulosa cell malignancy. We postulate that this presentation may be due to the 
      novel menin gene mutation recently described.
FAU - Hall, Michael J
AU  - Hall MJ
AD  - Department of Clinical Genetics, Fox Chase Cancer Center, Philadelphia, PA, USA.
FAU - Innocent, Julie
AU  - Innocent J
AD  - Department of Medical Oncology, Fox Chase Cancer Center, Philadelphia, PA, USA.
FAU - Rybak, Christina
AU  - Rybak C
AD  - Department of Clinical Genetics, Fox Chase Cancer Center, Philadelphia, PA, USA.
FAU - Veloski, Colleen
AU  - Veloski C
AD  - Department of Internal Medicine, Fox Chase Cancer Center, Philadelphia, PA, USA.
FAU - Scott, Walter J
AU  - Scott WJ
AD  - Department of Surgical Oncology, Fox Chase Cancer Center, Philadelphia, PA, USA.
FAU - Wu, Hong
AU  - Wu H
AD  - Department of Pathology, Fox Chase Cancer Center, Philadelphia, PA, USA.
FAU - Ridge, John A
AU  - Ridge JA
AD  - Department of Surgical Oncology, Fox Chase Cancer Center, Philadelphia, PA, USA.
FAU - Hoffman, John P
AU  - Hoffman JP
AD  - Department of Surgical Oncology, Fox Chase Cancer Center, Philadelphia, PA, USA.
FAU - Borghaei, Hossein
AU  - Borghaei H
AD  - Department of Medical Oncology, Fox Chase Cancer Center, Philadelphia, PA, USA.
FAU - Turaka, Aruna
AU  - Turaka A
AD  - Department of Radiation Oncology, Fox Chase Cancer Center, Philadelphia, PA, USA.
FAU - Daly, Mary B
AU  - Daly MB
AD  - Department of Clinical Genetics, Fox Chase Cancer Center, Philadelphia, PA, USA.
LA  - eng
PT  - Case Reports
DEP - 20150217
PL  - New Zealand
TA  - Appl Clin Genet
JT  - The application of clinical genetics
JID - 101579789
PMC - PMC4337709
OTO - NOTNLM
OT  - hyperparathyroidism
OT  - menin gene
OT  - ovarian tumors
EDAT- 2015/03/04 06:00
MHDA- 2015/03/04 06:01
PMCR- 2015/02/17
CRDT- 2015/03/04 06:00
PHST- 2015/03/04 06:00 [entrez]
PHST- 2015/03/04 06:00 [pubmed]
PHST- 2015/03/04 06:01 [medline]
PHST- 2015/02/17 00:00 [pmc-release]
AID - tacg-8-069 [pii]
AID - 10.2147/TACG.S72223 [doi]
PST - epublish
SO  - Appl Clin Genet. 2015 Feb 17;8:69-73. doi: 10.2147/TACG.S72223. eCollection 2015.