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

Judit Dénes; Francesca Swords; Eleanor Rattenberry; Karen Stals; Martina Owens; Treena Cranston; Paraskevi Xekouki; Linda Moran; Ajith Kumar; Christopher Wassif; Naomi Fersht; Stephanie E Baldeweg; Damian Morris; Stafford Lightman; Amar Agha; Aled Rees; Joan Grieve; Michael Powell; Cesar Luiz Boguszewski; Pinaki Dutta; Rajesh V Thakker; Umasuthan Srirangalingam; Chris J Thompson; Maralyn Druce; Claire Higham; Julian Davis; Rosalind Eeles; Mark Stevenson; Brendan O'Sullivan; Phillipe Taniere; Kassiani Skordilis; Plamena Gabrovska; Anne Barlier; Susan M Webb; Anna Aulinas; William M Drake; John S Bevan; Cristina Preda; Nadezhda Dalantaeva; Antônio Ribeiro-Oliveira; Isabel Tena Garcia; Galina Yordanova; Violeta Iotova; Jane Evanson; Ashley B Grossman; Jacqueline Trouillas; Sian Ellard; Constantine A Stratakis; Eamonn R Maher; Federico Roncaroli; Márta Korbonits

doi:10.1210/jc.2014-3399

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

Judit Dénes, Francesca Swords, Eleanor Rattenberry, Karen Stals, Martina Owens, Treena Cranston, Paraskevi Xekouki, Linda Moran, Ajith Kumar, Christopher Wassif, Naomi Fersht, Stephanie E Baldeweg, Damian Morris, Stafford Lightman, Amar Agha, Aled Rees, Joan Grieve, Michael Powell, Cesar Luiz Boguszewski, Pinaki DuttaRajesh V Thakker, Umasuthan Srirangalingam, Chris J Thompson, Maralyn Druce, Claire Higham, Julian Davis, Rosalind Eeles, Mark Stevenson, Brendan O'Sullivan, Phillipe Taniere, Kassiani Skordilis, Plamena Gabrovska, Anne Barlier, Susan M Webb, Anna Aulinas, William M Drake, John S Bevan, Cristina Preda, Nadezhda Dalantaeva, Antônio Ribeiro-Oliveira, Isabel Tena Garcia, Galina Yordanova, Violeta Iotova, Jane Evanson, Ashley B Grossman, Jacqueline Trouillas, Sian Ellard, Constantine A Stratakis, Eamonn R Maher, Federico Roncaroli, Márta Korbonits

Research output: Contribution to journal › Article (Academic Journal) › peer-review

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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: 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.

Original language	English
Pages (from-to)	E531-41
Journal	Journal of Clinical Endocrinology and Metabolism
Volume	100
Issue number	3
DOIs	https://doi.org/10.1210/jc.2014-3399
Publication status	Published - Mar 2015

Keywords

Adenoma/epidemiology
Adrenal Gland Neoplasms/epidemiology
Adult
Cohort Studies
Female
Genetic Association Studies
Genetic Heterogeneity
Genetic Predisposition to Disease
Genetic Testing
Humans
Male
Middle Aged
Paraganglioma/epidemiology
Pheochromocytoma/epidemiology
Pituitary Neoplasms/epidemiology
Young Adult

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Dénes, J., Swords, F., Rattenberry, E., Stals, K., Owens, M., 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., ... Korbonits, M. (2015). Heterogeneous genetic background of the association of pheochromocytoma/paraganglioma and pituitary adenoma: results from a large patient cohort. Journal of Clinical Endocrinology and Metabolism, 100(3), E531-41. https://doi.org/10.1210/jc.2014-3399

@article{5318eed7a0014f48bae29f0e936994f8,

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

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.",

keywords = "Adenoma/epidemiology, Adrenal Gland Neoplasms/epidemiology, Adult, Cohort Studies, Female, Genetic Association Studies, Genetic Heterogeneity, Genetic Predisposition to Disease, Genetic Testing, Humans, Male, Middle Aged, Paraganglioma/epidemiology, Pheochromocytoma/epidemiology, Pituitary Neoplasms/epidemiology, Young Adult",

author = "Judit D{\'e}nes and Francesca Swords and Eleanor Rattenberry and Karen Stals and Martina Owens and Treena Cranston and Paraskevi Xekouki and Linda Moran and Ajith Kumar and Christopher Wassif and Naomi Fersht and Baldeweg, {Stephanie E} and Damian Morris and Stafford Lightman and Amar Agha and Aled Rees and Joan Grieve and Michael Powell and Boguszewski, {Cesar Luiz} and Pinaki Dutta and Thakker, {Rajesh V} and Umasuthan Srirangalingam and Thompson, {Chris J} and Maralyn Druce and Claire Higham and Julian Davis and Rosalind Eeles and Mark Stevenson and Brendan O'Sullivan and Phillipe Taniere and Kassiani Skordilis and Plamena Gabrovska and Anne Barlier and Webb, {Susan M} and Anna Aulinas and Drake, {William M} and Bevan, {John S} and Cristina Preda and Nadezhda Dalantaeva and Ant{\^o}nio Ribeiro-Oliveira and Garcia, {Isabel Tena} and Galina Yordanova and Violeta Iotova and Jane Evanson and Grossman, {Ashley B} and Jacqueline Trouillas and Sian Ellard and Stratakis, {Constantine A} and Maher, {Eamonn R} and Federico Roncaroli and M{\'a}rta Korbonits",

year = "2015",

month = mar,

doi = "10.1210/jc.2014-3399",

language = "English",

volume = "100",

pages = "E531--41",

journal = "Journal of Clinical Endocrinology and Metabolism",

issn = "0021-972X",

publisher = "Oxford University Press",

number = "3",

}

Dénes, J, Swords, F, Rattenberry, E, Stals, K, Owens, M, Cranston, T, Xekouki, P, Moran, L, Kumar, A, Wassif, C, Fersht, N, Baldeweg, SE, Morris, D, Lightman, S, Agha, A, Rees, A, Grieve, J, Powell, M, Boguszewski, CL, Dutta, P, Thakker, RV, Srirangalingam, U, Thompson, CJ, Druce, M, Higham, C, Davis, J, Eeles, R, Stevenson, M, O'Sullivan, B, Taniere, P, Skordilis, K, Gabrovska, P, Barlier, A, Webb, SM, Aulinas, A, Drake, WM, Bevan, JS, Preda, C, Dalantaeva, N, Ribeiro-Oliveira, A, Garcia, IT, Yordanova, G, Iotova, V, Evanson, J, Grossman, AB, Trouillas, J, Ellard, S, Stratakis, CA, Maher, ER, Roncaroli, F & Korbonits, M 2015, 'Heterogeneous genetic background of the association of pheochromocytoma/paraganglioma and pituitary adenoma: results from a large patient cohort', Journal of Clinical Endocrinology and Metabolism, vol. 100, no. 3, pp. E531-41. https://doi.org/10.1210/jc.2014-3399

Heterogeneous genetic background of the association of pheochromocytoma/paraganglioma and pituitary adenoma: results from a large patient cohort. / Dénes, Judit; Swords, Francesca; Rattenberry, Eleanor et al.
In: Journal of Clinical Endocrinology and Metabolism, Vol. 100, No. 3, 03.2015, p. E531-41.

Research output: Contribution to journal › Article (Academic Journal) › peer-review

TY - JOUR

T1 - Heterogeneous genetic background of the association of pheochromocytoma/paraganglioma and pituitary adenoma

T2 - results from a large patient cohort

AU - Dénes, Judit

AU - Swords, Francesca

AU - Rattenberry, Eleanor

AU - Stals, Karen

AU - Owens, Martina

AU - Cranston, Treena

AU - Xekouki, Paraskevi

AU - Moran, Linda

AU - Kumar, Ajith

AU - Wassif, Christopher

AU - Fersht, Naomi

AU - Baldeweg, Stephanie E

AU - Morris, Damian

AU - Lightman, Stafford

AU - Agha, Amar

AU - Rees, Aled

AU - Grieve, Joan

AU - Powell, Michael

AU - Boguszewski, Cesar Luiz

AU - Dutta, Pinaki

AU - Thakker, Rajesh V

AU - Srirangalingam, Umasuthan

AU - Thompson, Chris J

AU - Druce, Maralyn

AU - Higham, Claire

AU - Davis, Julian

AU - Eeles, Rosalind

AU - Stevenson, Mark

AU - O'Sullivan, Brendan

AU - Taniere, Phillipe

AU - Skordilis, Kassiani

AU - Gabrovska, Plamena

AU - Barlier, Anne

AU - Webb, Susan M

AU - Aulinas, Anna

AU - Drake, William M

AU - Bevan, John S

AU - Preda, Cristina

AU - Dalantaeva, Nadezhda

AU - Ribeiro-Oliveira, Antônio

AU - Garcia, Isabel Tena

AU - Yordanova, Galina

AU - Iotova, Violeta

AU - Evanson, Jane

AU - Grossman, Ashley B

AU - Trouillas, Jacqueline

AU - Ellard, Sian

AU - Stratakis, Constantine A

AU - Maher, Eamonn R

AU - Roncaroli, Federico

AU - Korbonits, Márta

PY - 2015/3

Y1 - 2015/3

N2 - 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.

AB - 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.

KW - Adenoma/epidemiology

KW - Adrenal Gland Neoplasms/epidemiology

KW - Adult

KW - Cohort Studies

KW - Female

KW - Genetic Association Studies

KW - Genetic Heterogeneity

KW - Genetic Predisposition to Disease

KW - Genetic Testing

KW - Humans

KW - Male

KW - Middle Aged

KW - Paraganglioma/epidemiology

KW - Pheochromocytoma/epidemiology

KW - Pituitary Neoplasms/epidemiology

KW - Young Adult

U2 - 10.1210/jc.2014-3399

DO - 10.1210/jc.2014-3399

M3 - Article (Academic Journal)

C2 - 25494863

SN - 0021-972X

VL - 100

SP - E531-41

JO - Journal of Clinical Endocrinology and Metabolism

JF - Journal of Clinical Endocrinology and Metabolism

IS - 3

ER -

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

Abstract

Keywords

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