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

2.50
Hdl Handle:
http://hdl.handle.net/11287/593931
Title:
Heterogeneous genetic background of the association of pheochromocytoma/paraganglioma and pituitary adenoma: results from a large patient cohort
Authors:
Denes, J.; Swords, F.; Rattenberry, E.; Stals, Karen; Owens, Martina; Cranston, T.; Xekouki, P.; Moran, L.; Kumar, A.; Wassif, C.; Fersht, N.; Baldeweg, S. E.; Morris, D.; Lightman, S.; Agha, A.; Rees, A.; Grieve, J.; Powell, M.; Boguszewski, C. L.; Dutta, P.; Thakker, R. V.; Srirangalingam, U.; Thompson, C. J.; Druce, M.; Higham, C.; Davis, J.; Eeles, R.; Stevenson, M.; O'Sullivan, B.; Taniere, P.; Skordilis, K.; Gabrovska, P.; Barlier, A.; Webb, S. M.; Aulinas, A.; Drake, W. M.; Bevan, J. S.; Preda, C.; Dalantaeva, N.; Ribeiro-Oliveira, A., Jr.; Garcia, I. T.; Yordanova, G.; Iotova, V.; Evanson, J.; Grossman, A. B.; Trouillas, J.; Ellard, Sian ( 0000-0002-7620-5526 ) ; Stratakis, C. A.; Maher, E. R.; Roncaroli, F.; Korbonits, M.
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: The objective of the investigation was 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, FH) 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: The study was conducted at university hospitals. PATIENTS: Thirty-nine patients with sporadic of familial pituitary adenoma and pheo/PGL participated in the study. OUTCOME: Outcomes included genetic screening and clinical characteristics. RESULTS: Eleven germline mutations (five SDHB, one SDHC, one SDHD, two VHL, and two MEN1) and four variants of unknown significance (two SDHA, one SDHB, and one SDHAF2) were identified in the studied genes in our patient cohort. Tumor tissue analysis identified LOH at the SDHB locus in three pituitary adenomas and loss of heterozygosity at the MEN1 locus in two pheochromocytomas. All the pituitary adenomas of patients affected by SDHX alterations have a 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, whereas 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.
Citation:
J Clin Endocrinol Metab. 2015 Mar;100(3):E531-41.
Publisher:
Endocrine Society
Journal:
The Journal of clinical endocrinology and metabolism
Issue Date:
1-Mar-2015
URI:
http://hdl.handle.net/11287/593931
DOI:
10.1210/jc.2014-3399
PubMed ID:
25494863
Additional Links:
http://www.ncbi.nlm.nih.gov/pmc/articles/pmid/25494863/
Note:
This article is available via Open Access. Please click on the 'Additional Link' above to access the full-text.
Type:
Journal Article; Research Support, Non-U.S. Gov't
Language:
eng
ISSN:
1945-7197
Appears in Collections:
2015 RD&E publications; Molecular Genetics; Molecular Genetics; Research & Development staff

Full metadata record

DC FieldValue Language
dc.contributor.authorDenes, J.en
dc.contributor.authorSwords, F.en
dc.contributor.authorRattenberry, E.en
dc.contributor.authorStals, Karenen
dc.contributor.authorOwens, Martinaen
dc.contributor.authorCranston, T.en
dc.contributor.authorXekouki, P.en
dc.contributor.authorMoran, L.en
dc.contributor.authorKumar, A.en
dc.contributor.authorWassif, C.en
dc.contributor.authorFersht, N.en
dc.contributor.authorBaldeweg, S. E.en
dc.contributor.authorMorris, D.en
dc.contributor.authorLightman, S.en
dc.contributor.authorAgha, A.en
dc.contributor.authorRees, A.en
dc.contributor.authorGrieve, J.en
dc.contributor.authorPowell, M.en
dc.contributor.authorBoguszewski, C. L.en
dc.contributor.authorDutta, P.en
dc.contributor.authorThakker, R. V.en
dc.contributor.authorSrirangalingam, U.en
dc.contributor.authorThompson, C. J.en
dc.contributor.authorDruce, M.en
dc.contributor.authorHigham, C.en
dc.contributor.authorDavis, J.en
dc.contributor.authorEeles, R.en
dc.contributor.authorStevenson, M.en
dc.contributor.authorO'Sullivan, B.en
dc.contributor.authorTaniere, P.en
dc.contributor.authorSkordilis, K.en
dc.contributor.authorGabrovska, P.en
dc.contributor.authorBarlier, A.en
dc.contributor.authorWebb, S. M.en
dc.contributor.authorAulinas, A.en
dc.contributor.authorDrake, W. M.en
dc.contributor.authorBevan, J. S.en
dc.contributor.authorPreda, C.en
dc.contributor.authorDalantaeva, N.en
dc.contributor.authorRibeiro-Oliveira, A., Jr.en
dc.contributor.authorGarcia, I. T.en
dc.contributor.authorYordanova, G.en
dc.contributor.authorIotova, V.en
dc.contributor.authorEvanson, J.en
dc.contributor.authorGrossman, A. B.en
dc.contributor.authorTrouillas, J.en
dc.contributor.authorEllard, Sianen
dc.contributor.authorStratakis, C. A.en
dc.contributor.authorMaher, E. R.en
dc.contributor.authorRoncaroli, F.en
dc.contributor.authorKorbonits, M.en
dc.date.accessioned2016-01-19T12:37:30Zen
dc.date.available2016-01-19T12:37:30Zen
dc.date.issued2015-03-01en
dc.identifier.citationJ Clin Endocrinol Metab. 2015 Mar;100(3):E531-41.en
dc.identifier.issn1945-7197en
dc.identifier.pmid25494863en
dc.identifier.doi10.1210/jc.2014-3399en
dc.identifier.urihttp://hdl.handle.net/11287/593931en
dc.description.abstractCONTEXT: 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: The objective of the investigation was 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, FH) 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: The study was conducted at university hospitals. PATIENTS: Thirty-nine patients with sporadic of familial pituitary adenoma and pheo/PGL participated in the study. OUTCOME: Outcomes included genetic screening and clinical characteristics. RESULTS: Eleven germline mutations (five SDHB, one SDHC, one SDHD, two VHL, and two MEN1) and four variants of unknown significance (two SDHA, one SDHB, and one SDHAF2) were identified in the studied genes in our patient cohort. Tumor tissue analysis identified LOH at the SDHB locus in three pituitary adenomas and loss of heterozygosity at the MEN1 locus in two pheochromocytomas. All the pituitary adenomas of patients affected by SDHX alterations have a 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, whereas 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.en
dc.language.isoengen
dc.publisherEndocrine Societyen
dc.relation.urlhttp://www.ncbi.nlm.nih.gov/pmc/articles/pmid/25494863/en
dc.titleHeterogeneous genetic background of the association of pheochromocytoma/paraganglioma and pituitary adenoma: results from a large patient cohorten
dc.typeJournal Articleen
dc.typeResearch Support, Non-U.S. Gov'ten
dc.identifier.journalThe Journal of clinical endocrinology and metabolismen
dc.description.noteThis article is available via Open Access. Please click on the 'Additional Link' above to access the full-text.en

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