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Heterogeneous genetic background of the association of pheochromocytoma/paraganglioma and pituitary adenoma - results from a large patient cohort.

Dénes, J
; 
Swords, F
; 
Rattenberry, E
; 
Stals, K
; 
Owens, M
; 
Cranston, T
; 
Xekouki, P
; 
Moran, L
; 
Kumar, A
; 
Wassif, C
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Abstract
Context: Pituitary adenomas and pheochromocytomas/paragangliomas (pheo/PGL) can occur in the same patient or in the same family. Coexistence of the two diseases could be due to either a common pathogenic mechanism or a coincidence. Objective: To study the possible coexistence of pituitary adenoma and pheo/PGL. Design: Thirty-nine cases of sporadic or familial pheo/PGL and pituitary adenomas were investigated. Known pheo/PGL genes (SDHA-D, SDHAF2, RET, VHL, TMEM127, MAX) and pituitary adenoma genes (MEN1, AIP, CDKN1B) were sequenced using next generation or Sanger sequencing. Loss of heterozygosity study and pathological studies were performed on the available tumor samples. Setting: University hospitals. Patients: Thirty-nine patients with sporadic of familial pituitary adenoma and pheo/PGL. Outcome: Genetic screening and clinical characteristics. Results: Eleven germline mutations (5 SDHB, 1 SDHC, 1 SDHD, 2 VHL and 2 MEN1) and four variants of unknown significance (2 SDHA, a SDHB, and a SDHAF2) were identified in the studied genes in our patient cohort. Tumor tissue analysis identified LOH at the SDHB locus in 3 pituitary adenomas and LOH at the MEN1 locus in 2 pheochromocytomas. All the pituitary adenomas of patients affected by SDHX alterations have unique histological feature not previously described in this context. Conclusions: Mutations in the genes known to cause pheo/PGL can rarely be associated with pituitary adenomas, while mutation in a gene predisposing to pituitary adenomas (MEN1) can be associated with pheo/PGL. Our findings suggest that genetic testing should be considered in all patients or families with the constellation of pheo/PGL and a pituitary adenoma.
Authors
Dénes, J
Swords, F
Rattenberry, E
Stals, K
Owens, M
Cranston, T
Xekouki, P
Moran, L
Kumar, A
Wassif, C
Fersht, N
Baldeweg, S
Morris, D
Lightman, S
Agha, A
Rees, A
Grieve, J
Powell, M
Luiz Boguszewski, C
Dutta, P
Thakker, R
Srirangalingam, U
Thompson, C
Druce, M
Higham, Claire E
Davis, J
Eeles, R
Stevenson, M
O'Sullivan, B
Taniere, P
Skordilis, K
Gabrovska, P
Barlier, A
Webb, S
Aulinas, A
Drake, W
Bevan, J
Preda, C
Dalantaeva, N
Ribeiro-Oliveira, A
Tena Garcia, I
Yordanova, G
Iotova, V
Evanson, J
Grossman, A
Trouillas, J
Ellard, S
Stratakis, C
Maher, E
Roncaroli, F
Korbonits, M
Affiliation
Department of Endocrinology, Barts and the London School of Medicine, Queen Mary University of London, London, UK
Description
Date
2014-12-12
Publisher
Collections
All Christie Publications
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Keywords
Type
Article
Citation
Heterogeneous genetic background of the association of pheochromocytoma/paraganglioma and pituitary adenoma - results from a large patient cohort. 2014:jc20143399 J Clin Endocrinol Metab
Journal Title
Journal ISSN
Volume Title
URI
http://hdl.handle.net/10541/337956
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