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VOLUME 19 , ISSUE 2 ( July-December, 2024 ) > List of Articles

REVIEW ARTICLE

MEN 5: The New Kid on the Block—A Comprehensive Narrative Review

Gopal Puri, Kanika Sharma, Reva S Sahu, Piyush Ranjan, Brijesh K Singh

Keywords : MEN 5, Multiple endocrine neoplasia, Paraganglioma, Pheochromocytoma, Pituitary adenoma

Citation Information : Puri G, Sharma K, Sahu RS, Ranjan P, Singh BK. MEN 5: The New Kid on the Block—A Comprehensive Narrative Review. 2024; 19 (2):65-69.

DOI: 10.5005/jp-journals-10088-11242

License: CC BY-NC 4.0

Published Online: 20-12-2024

Copyright Statement:  Copyright © 2024; The Author(s).


Abstract

In addition to the recognized types of multiple endocrine neoplasia (MEN) syndromes (MEN 1, MEN 2a, and MEN 2b), MEN 4 was described relatively recently, and there is now a proposition of a fifth variety. It has been recognized as an independent syndrome by the 5th edition of the WHO Classification of Endocrine and Neuroendocrine Tumors as well as the 5th edition of the Genetic Tumor Syndromes. Multiple endocrine neoplasia type 5 (MEN 5) is caused by a pathogenic mutation in MYC associated factor X (MAX) gene, which is a tumor suppressor gene. The endocrine manifestations include tumors of the adrenal, pituitary, parathyroid, and pancreas. The non-endocrine tumors include renal cell carcinoma, renal oncocytoma, and carcinoma of the lung. This article thoroughly reviews the available literature and tries to understand the journey of discovery of a new syndrome in endocrine surgery.

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  1. Burnichon N, Cascón A, Schiavi F, et al. MAX mutations cause hereditary and sporadic pheochromocytoma and paraganglioma. Clin Cancer Res 2012;18(10):2828–2837. DOI: 10.1158/1078-0432.CCR-12-0160.
  2. Comino-Méndez I, Gracia-Aznárez FJ, Schiavi F, et al. Exome sequencing identifies MAX mutations as a cause of hereditary pheochromocytoma. Nat Genet 2011;43(7):663–667. DOI: 10.1038/ng.861.
  3. Kohl NE, Kanda N, Schreck RR, et al. Transposition and amplification of oncogene-related sequences in human neuroblastomas. Cell 1983;35(2):359–367. DOI: 10.1016/0092-8674(83)90169-1.
  4. Ferrara AM, Lombardi G, Pambuku A, et al. Temozolomide treatment of a malignant pheochromocytoma and an unresectable MAX-related paraganglioma. Anticancer drugs 2018;29(1):102–105. DOI: 10.1097/CAD.0000000000000570.
  5. Shibata M, Inaishi T, Miyajima N, et al. Synchronous bilateral pheochromocytomas and paraganglioma with novel germline mutation in MAX: A case report. Surg Cas Rep 2017;3:1–5. DOI: 10.1186/s40792-017-0408-x.
  6. Roszko KL, Blouch E, Blake M, et al. Case report of a prolactinoma in a patient with a novel MAX mutation and bilateral pheochromocytomas. J Endocr Soc 2017;1(11):1401–1407. DOI: 10.1210/js.2017- 00135.
  7. Daly AF, Castermans E, Oudijk L, et al. Pheochromocytomas and pituitary adenomas in three patients with MAX exon deletions. Endocr Relat Cancer 2018;25(5):L37–L42. DOI: 10.1530/ERC-18-0065.
  8. Xekouki P, Szarek E, Bullova P, et al. Pituitary adenoma with paraganglioma/pheochromocytoma (3PAs) and succinate dehydrogenase defects in humans and mice. J Clin Endocrin Metab 2015;100(5):E710–E719. DOI: 10.1210/jc.2014-4297.
  9. Pozza C, Sesti F, Di Dato C, et al. A novel MAX gene mutation variant in a patient with multiple and “composite” neuroendocrine–neuroblastic tumors. Front Endocrinol 2020;11:234. DOI: 10.3389/fendo.2020.00234.
  10. Petignot S, Daly AF, Castermans E, et al. Pancreatic neuroendocrine neoplasm associated with a familial MAX deletion. Horm Metab Res 2020;52(11):784–787. DOI: 10.1055/a-1186-0790.
  11. Seabrook AJ, Harris JE, Velosa SB, et al. Multiple endocrine tumors associated with germline MAX mutations: Multiple endocrine neoplasia type 5? J Clin Endocrin Metab 2021;106(4):e1163–e1182. DOI: 10.1210/clinem/dgaa957.
  12. Charoenngam N, Likasitwatanakul P, Kansuttiviwat C, et al. THU613 multiple endocrine neoplasia type 5 associated with germline max mutations—new insights into this proposed entity. J Endocr Soc 2023;7(Supplement_1):114–143. DOI: 10.1210/jendso/bvad114.143.
  13. Taïeb D, Jha A, Guerin C, et al. 18F-FDOPA PET/CT imaging of MAX-related pheochromocytoma. J Clin Endocrin Metab 2018;103(4): 1574–1582. DOI: 10.1210/jc.2017-02324.
  14. Atchley WR, Fitch WM. Myc and Max: Molecular evolution of a family of proto-oncogene products and their dimerization partner. Proc Natl Acad Sci U S A 1995;92(22):10217–10221. DOI: 10.1073/pnas.92.22.10217.
  15. Casey RT, Warren AY, Martin JE, et al. Clinical and molecular features of renal and pheochromocytoma/paraganglioma tumor association syndrome (RAPTAS): Case series and literature review. J Clin Endocrin Metab 2017;102(11):4013–4022. DOI: 10.1210/jc.2017-00562.
  16. Cascón A, Robledo M. MAX and MYC: A heritable breakup. Cancer Res 2012;72(13):3119–3124. DOI: 10.1158/0008-5472.CAN-11-3891.
  17. Berg T, Cohen SB, Desharnais J, et al. Small-molecule antagonists of Myc/Max dimerization inhibit Myc-induced transformation of chicken embryo fibroblasts. PNAS 2002;99(6):3830–3835. DOI: 10.1073/pnas.062036999.
  18. Zhu J, Blenis J, Yuan J. Activation of PI3K/Akt and MAPK pathways regulates Myc-mediated transcription by phosphorylating and promoting the degradation of Mad1. Proc Natl Acad Sci U S A 2008;105(18):6584–6589. DOI: 10.1073/pnas.0802785105.
  19. Nair SK, Burley SK. X-ray structures of Myc-Max and Mad-Max recognizing DNA: Molecular bases of regulation by proto-oncogenic transcription factors. Cell 2003;112(2):193–205. DOI: 10.1016/s0092-8674(02)01284-9.
  20. Grandori C, Cowley SM, James LP, et al. The Myc/Max/Mad network and the transcriptional control of cell behavior. Annu Rev Cell Dev Biol 2000;16(1):653–699. DOI: 10.1146/annurev.cellbio.16.1.653.
  21. Gallant P, Steiger D. Myc's secret life without Max. Cell Cycle 2009;8(23):3848–3853. DOI: 10.4161/cc.8.23.10088.
  22. Qin N, De Cubas AA, Garcia-Martin R, et al. Opposing effects of HIF1α and HIF2α on chromaffin cell phenotypic features and tumor cell proliferation: Insights from MYC-associated factor X. Inter J cancer 2014;135(9):2054–2064. DOI: 10.1002/ijc.28868.
  23. Bausch B, Schiavi F, Ni Y, et al. Clinical characterization of the pheochromocytoma and paraganglioma susceptibility genes SDHA, TMEM127, MAX, and SDHAF2 for gene-informed prevention. JAMA Oncol 2017;3(9):1204–1212. DOI: 10.1001/jamaoncol.2017.0223.
  24. Korpershoek E, Koffy D, Eussen BH, et al. Complex MAX rearrangement in a family with malignant pheochromocytoma, renal oncocytoma, and erythrocytosis. J Clin Endocrin Metab 2016;101(2):453–460. DOI: 10.1210/jc.2015-2592.
  25. Cancer Genome Atlas Research Network. Comprehensive molecular profiling of lung adenocarcinoma. Nature 2014;511(7511):543. DOI: 10.1038/nature13385.
  26. Grogan RH, Pacak K, Pasche L, et al. Bilateral adrenal medullary hyperplasia associated with an SDHB mutation. J Clin Oncol 2011;29(8):e200–e202. DOI: 10.1200/JCO.2010.32.2156.
  27. Romanet P, Guerin C, Pedini P, et al. Pathological and genetic characterization of bilateral adrenomedullary hyperplasia in a patient with germline MAX mutation. Endocr Pathol 2017;28:302–307. DOI: 10.1007/s12022-016-9460-5.
  28. Cheung VK, Gill AJ, Chou A. Old, new, and emerging immunohistochemical markers in pheochromocytoma and paraganglioma. Endocr pathol 2018;29:169–175. DOI: 10.1007/s12022-018-9534-7.
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