Heterogeneous Genetic Background of the Association of Pheochromocytoma/Paraganglioma and Pituitary Adenoma: Results From a Large Patient Cohort

被引：113

作者：

Denes, Judit ^{[1
,2
,3
]}

Swords, Francesca ^{[4
]}

Rattenberry, Eleanor

Stals, Karen ^{[6
]}

Owens, Martina ^{[6
]}

Cranston, Treena ^{[8
]}

Xekouki, Paraskevi ^{[9
]}

Moran, Linda ^{[11
]}

Kumar, Ajith ^{[12
]}

Wassif, Christopher ^{[10
]}

Fersht, Naomi ^{[13
]}

Baldeweg, Stephanie E. ^{[14
]}

Morris, Damian ^{[15
]}

Lightman, Stafford ^{[16
]}

Agha, Amar ^{[17
]}

Rees, Aled ^{[18
]}

Grieve, Joan ^{[19
]}

Powell, Michael ^{[19
]}

Boguszewski, Cesar Luiz ^{[20
]}

Dutta, Pinaki ^{[21
]}

Thakker, Rajesh V. ^{[22
]}

Srirangalingam, Umasuthan ^{[1
,2
]}

Thompson, Chris J. ^{[17
]}

Druce, Maralyn ^{[1
,2
]}

Higham, Claire ^{[23
]}

Davis, Julian ^{[24
,25
]}

Eeles, Rosalind ^{[26
]}

Stevenson, Mark ^{[22
]}

O'Sullivan, Brendan ^{[27
]}

Taniere, Phillipe ^{[27
]}

Skordilis, Kassiani ^{[27
]}

Gabrovska, Plamena ^{[1
,2
]}

Barlier, Anne ^{[28
]}

Webb, Susan M. ^{[29
]}

Aulinas, Anna ^{[29
]}

Drake, William M. ^{[1
,2
]}

Bevan, John S. ^{[30
]}

Preda, Cristina ^{[31
]}

Dalantaeva, Nadezhda ^{[32
]}

Ribeiro-Oliveira, Antonio, Jr. ^{[33
]}

Garcia, Isabel Tena ^{[34
]}

Yordanova, Galina ^{[35
]}

Iotova, Violeta ^{[35
]}

Evanson, Jane ^{[36
]}

Grossman, Ashley B. ^{[37
]}

Trouillas, Jacqueline ^{[38
]}

Ellard, Sian ^{[6
,7
]}

Stratakis, Constantine A. ^{[9
]}

Maher, Eamonn R. ^{[5
,39
]}

Roncaroli, Federico ^{[5
,40
]}

机构：

[1] Queen Mary Univ London, Barts, Dept Endocrinol, London EC1M 6BQ, England

[2] Queen Mary Univ London, London Sch Med, London EC1M 6BQ, England

[3] Semmelweis Univ, Sch PhD Studies, Sch Clin Med, H-1085 Budapest, Hungary

[4] Norfolk & Norwich Univ Hosp, Endocrinol Directorate, Norwich NR4 7UZ, Norfolk, England

[5] Univ Birmingham, Dept Med & Mol Genet, Birmingham B15 2TT, W Midlands, England

[6] Royal Devon, Dept Mol Genet, Exeter EX2 5DW, Devon, England

[7] Univ Exeter, Sch Med, Exeter EX4 4PY, Devon, England

[8] Univ Oxford, Churchill Hosp, Hosp Natl Hlth Serv Trust, Oxford Med Genet Labs, Oxford OX3 7LJ, England

[9] Eunice Kennedy Shriver Inst Child Hlth & Human De, Sect Endocrinol & Genet, NIH, Bethesda, MD 20892 USA

[10] Eunice Kennedy Shriver Inst Child Hlth & Human De, Sect Mol Dysmorphol, NIH, Bethesda, MD 20892 USA

[11] Imperial Coll Healthcare Natl Hlth Serv Trust, Charing Cross Hosp, Dept Histopathol, Elect Microscopy Unit, London W6 8RF, England

[12] Great Ormond St Hosp Sick Children, Dept Clin Genet, London WC1N 1LE, England

[13] UCL, Dept Oncol, London WC1E 6BT, England

[14] UCL, Dept Endocrinol, London WC1E 6BT, England

[15] Ipswich Hosp Natl Hlth Serv Trust, Dept Endocrinol & Diabet, Ipswich IP4 5PD, Suffolk, England

[16] Univ Bristol, Henry Wellcome Labs Integrat Neurosci & Endocrino, Bristol BS1 3NY, Avon, England

[17] Beaumont Hosp, Dept Endocrinol, Dublin 9, Ireland

[18] Cardiff Univ, Inst Mol & Expt Med, Cardiff CF10 3US, S Glam, Wales

[19] Natl Hosp Neurol & Neurosurg, Dept Neurosurg, London WC1N 3BG, England

[20] Univ Fed Parana, Hosp Clin, Serv Endocrinol & Metabol, BR-80210 Curitiba, Parana, Brazil

[21] Post Grad Inst Med Educ & Res, Dept Endocrinol, Chandigarh 160012, India

[22] Univ Oxford, Acad Endocrine Unit, Oxford OX1 3QX, England

[23] Christie Hosp Natl Hlth Serv Fdn Trust, Manchester M20 4BX, Lancs, England

[24] Univ Manchester, Fac Med & Human Sci, Ctr Endocrinol & Diabet, Inst Human Dev, Manchester M13 9PT, Lancs, England

[25] Manchester Acad, Hlth Sci Ctr, Cent Manchester Univ Hosp Natl Hlth Fdn Trust, Manchester Royal Infirm,Dept Endocrinol, Manchester M13 9WL, Lancs, England

[26] Inst Canc Res, Div Genet & Epidemiol, London SW7 3RP, England

[27] Univ Hosp Birmingham Natl Hlth Serv Fdn Trust, Dept Histopathol, Birmingham B29 6JD, W Midlands, England

[28] APHM Concept, Mol Biol Lab, F-7286 Marseille, France

[29] Hosp Sant Pau, Inst Salud Carlos III, Centro Invest Biomed Red Enfermedades Rara, Dept Endocrinol & Med,St Pau IIB, Madrid 28029, Spain

[30] Aberdeen Royal Infirm, JJR Macleod Ctr Diabet Endocrinol & Metab, Aberdeen AB25 2ZB, Scotland

[31] GrT Popa Univ Med & Pharm, Dept Endocrinol, Iasi 700115, Romania

[32] Lomonosov Moscow State Univ, Endocrinol Res Ctr, Moscow 115478, Russia

[33] Univ Fed Minas Gerais, Dept Internal Med, BR-30330120 Belo Horizonte, MG, Brazil

[34] Castellon Prov Hosp, Dept Med Oncol & Canc Genet, Castellon de La Plana 12002, Spain

[35] Univ Multiprofile Hosp Active Treatment St Marina, Dept Pediat & Med Genet, Varna, Bulgaria

[36] St Bartholomews Hosp, Dept Radiol, London E1 4NS, England

[37] Univ Oxford, Oxford Ctr Diabet Endocrinol & Metab, Oxford OX3 7LJ, England

[38] Univ Lyon, Hosp Civils Lyon, Ctr Pathol Est, INSERM Unite 1028, F-69622 Lyon, France

[39] Univ Cambridge, Dept Med Genet, Cambridge CB2 1TN, England

[40] Univ London Imperial Coll Sci Technol & Med, Div Brain Sci, London SW7 2AZ, England

来源：

JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM | 2015年 / 100卷 / 03期

关键词：

ENDOCRINE NEOPLASIA TYPE-1; HORMONE-RELEASING FACTOR; HIPPEL-LINDAU-DISEASE; B GENE; MUTATIONS; PARAGANGLIOMA; TUMORS; MITOCHONDRIA; PREVALENCE; DIAGNOSIS;

D O I：

10.1210/jc.2014-3399

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

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, where as 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.

引用

页码：E531 / E541

页数：11

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