{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,25]],"date-time":"2026-03-25T23:55:19Z","timestamp":1774482919151,"version":"3.50.1"},"reference-count":26,"publisher":"Georg Thieme Verlag KG","issue":"03","license":[{"start":{"date-parts":[[2026,3,25]],"date-time":"2026-03-25T00:00:00Z","timestamp":1774396800000},"content-version":"vor","delay-in-days":24,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100016778","name":"Paradifference\n                        foundation","doi-asserted-by":"crossref","award":["NA"],"award-info":[{"award-number":["NA"]}],"id":[{"id":"10.13039\/100016778","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Exp Clin Endocrinol Diabetes"],"published-print":{"date-parts":[[2026,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Succinate dehydrogenase (SDH) gene variants are the most common cause of the\n                        neuroendocrine tumour hereditary paraganglioma, which is associated with an\n                        over 20% metastasis risk as well as significant morbidity. There are\n                        currently no relevant human tumour cell lines or mouse models, and molecular\n                        understanding of downstream tumourigenic pathways is still rudimentary\n                        despite over two decades of concerted effort worldwide. These tumours\n                        generally show extremely slow in vivo doubling times (4\u201312 years),\n                        presumably existing in a primarily semi-quiescent state with little cell\n                        cycling or DNA replication. This characteristic makes deriving a useful\n                        tumour cell line impractical. A better alternative would be a cell line in\n                        which cell proliferation can be turned on and off at will, allowing\n                        expansion to generate sufficient cell numbers and experimentation once\n                        tumour cells have returned to their natural semi-quiescent state. The\n                        closest models currently available, highly-proliferating rat and mouse\n                        adrenal paraganglioma cell lines, are molecularly unrelated to SDH tumours.\n                        In this pilot study, we investigated whether primary SDH-derived\n                        paraganglioma tumour cells can be made to proliferate in vitro. We\n                        successfully transduced primary paraganglioma tumour cells with a lentiviral\n                        construct, using the proven strategy of c-MYC\u00acT58A (c-MYC) controlled by a\n                        Tet-On doxycycline-inducible expression system. We present the first\n                        evidence that primary paraganglioma chromaffin cells can be induced to\n                        proliferate in vitro, even in later passage cultures. Without any prior\n                        selection for chromaffin tumour cells, passaged cultures were obtained with\n                        over 80% synaptophysin-expressing chromaffin tumour cells, suggesting that\n                        this highly promising strategy deserves further exploration.<\/jats:p>","DOI":"10.1055\/a-2797-3576","type":"journal-article","created":{"date-parts":[[2026,3,25]],"date-time":"2026-03-25T23:30:26Z","timestamp":1774481426000},"page":"71-78","source":"Crossref","is-referenced-by-count":0,"title":["Pilot study: transduction of primary paraganglioma chromaffin tumour\n                    cells with inducible c-MYC drives cell proliferation"],"prefix":"10.1055","volume":"134","author":[{"given":"Juan","family":"Zhang","sequence":"additional","affiliation":[{"name":"Human Genetics, Leiden University Medical Center, Leiden,\n                    Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Heggert G.","family":"Rebel","sequence":"additional","affiliation":[{"name":"Human Genetics, Leiden University Medical Center, Leiden,\n                    Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dominique","family":"Duesman","sequence":"additional","affiliation":[{"name":"Human Genetics, Leiden University Medical Center, Leiden,\n                    Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Charlotte J.","family":"Dommering","sequence":"additional","affiliation":[{"name":"Human Genetics, Amsterdam UMC Location VUmc, Amsterdam,\n                    Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Abbey","family":"Schepers","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Leiden University\n                    Medical Center, Leiden, Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peter","family":"Devilee","sequence":"additional","affiliation":[{"name":"Human Genetics, Leiden University Medical Center, Leiden,\n                    Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jean-Pierre","family":"Bayley","sequence":"additional","affiliation":[{"name":"Human Genetics, Leiden University Medical Center, Leiden,\n                    Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"194","published-online":{"date-parts":[[2026,3,25]]},"reference":[{"key":"ref1","doi-asserted-by":"crossref","first-page":"5210","DOI":"10.1210\/jcem.86.11.8034","article-title":"Benign paragangliomas: clinical presentation and treatment outcomes in 236\n                    patients","volume":"86","author":"D Erickson","year":"2001","journal-title":"J Clin Endocrinol Metab"},{"key":"ref2","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1007\/s12022-022-09704-6","article-title":"Overview of the 2022 WHO Classification of Paragangliomas and\n                    Pheochromocytomas","volume":"33","author":"O Mete","year":"2022","journal-title":"Endocrine Pathology"},{"key":"ref3","doi-asserted-by":"crossref","first-page":"552","DOI":"10.1056\/NEJMra1806651","article-title":"Pheochromocytoma and Paraganglioma","volume":"381","author":"HP H Neumann","year":"2019","journal-title":"N Engl J Med"},{"key":"ref4","doi-asserted-by":"crossref","first-page":"R65","DOI":"10.1530\/EO-22-0044","article-title":"Pheochromocytoma and paraganglioma: germline genetics and hereditary\n                    syndromes","volume":"2","author":"C G Turin","year":"2022","journal-title":"Endocr Oncol"},{"key":"ref8","doi-asserted-by":"crossref","first-page":"2811","DOI":"10.1002\/1097-0142(20000615)88:12<2811::AID-CNCR21>3.0.CO;2-7","article-title":"Estimation of growth rate in patients with head and neck paragangliomas\n                    influences the treatment proposal","volume":"88","author":"J C Jansen","year":"2000","journal-title":"Cancer."},{"key":"ref9","doi-asserted-by":"crossref","first-page":"342","DOI":"10.4158\/EP161377.OR","article-title":"Growth Rate of Paragangliomas Related to Germline Mutations of the Sdhx\n                    Genes","volume":"23","author":"I Michalowska","year":"2017","journal-title":"Endocr Pract"},{"key":"ref10","doi-asserted-by":"crossref","first-page":"246","DOI":"10.1097\/01.MP.0000056982.07160.E3","article-title":"KI-67 AND hTERT expression can aid in the distinction between malignant and\n                    benign pheochromocytoma and paraganglioma","volume":"16","author":"E E Elder","year":"2003","journal-title":"Mod Pathol"},{"key":"ref12","doi-asserted-by":"crossref","first-page":"440","DOI":"10.1111\/cen.13434","article-title":"Outcomes of patients with metastatic phaeochromocytoma and paraganglioma: A\n                    systematic review and meta-analysis","volume":"87","author":"O Hamidi","year":"2017","journal-title":"Clin Endocrinol (Oxf)"},{"key":"ref13","doi-asserted-by":"crossref","first-page":"3296","DOI":"10.1210\/jc.2017-00992","article-title":"Malignant Pheochromocytoma and Paraganglioma: 272 Patients Over 55 Years","volume":"102","author":"O Hamidi","year":"2017","journal-title":"J Clin Endocrinol Metab"},{"key":"ref14","doi-asserted-by":"crossref","first-page":"768","DOI":"10.1136\/jmedgenet-2012-101192","article-title":"Risk of malignant paraganglioma in SDHB-mutation and SDHD-mutation carriers: a\n                    systematic review and meta-analysis","volume":"49","author":"L T van Hulsteijn","year":"2012","journal-title":"J Med Genet"},{"key":"ref15","doi-asserted-by":"crossref","first-page":"E551","DOI":"10.1016\/S2589-7500(23)00094-8","article-title":"Prediction of metastatic pheochromocytoma and paraganglioma: a machine learning\n                    modelling study using data from a cross-sectional cohort","volume":"5","author":"C Pamporaki","year":"2023","journal-title":"Lancet Digit Health"},{"key":"ref16","doi-asserted-by":"crossref","first-page":"1443","DOI":"10.1097\/HJH.0000000000002438","article-title":"Genetics, diagnosis, management and future directions of research of\n                    phaeochromocytoma and paraganglioma: a position statement and consensus of the\n                    Working Group on Endocrine Hypertension of the European Society of\n                    Hypertension","volume":"38","author":"JW M Lenders","year":"2020","journal-title":"Journal of Hypertension"},{"key":"ref17","doi-asserted-by":"crossref","first-page":"897","DOI":"10.1111\/jop.13286","article-title":"Paragangliomas of the head and neck","volume":"51","author":"C Valero","year":"2022","journal-title":"J Oral Pathol Med"},{"key":"ref18","doi-asserted-by":"crossref","first-page":"2963","DOI":"10.1210\/clinem\/dgac471","article-title":"Targeted Therapies in Pheochromocytoma and Paraganglioma","volume":"107","author":"K Wang","year":"2022","journal-title":"J Clin Endocr Metab"},{"key":"ref19","doi-asserted-by":"crossref","first-page":"739","DOI":"10.1016\/j.ccr.2013.04.018","article-title":"SDH mutations establish a hypermethylator phenotype in paraganglioma","volume":"23","author":"E Letouze","year":"2013","journal-title":"Cancer Cell"},{"key":"ref20","doi-asserted-by":"crossref","first-page":"e65624","DOI":"10.1371\/journal.pone.0065624","article-title":"Progenitor cell line (hPheo1) derived from a human pheochromocytoma tumor","volume":"8","author":"H K Ghayee","year":"2013","journal-title":"PLoS One"},{"key":"ref21","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1530\/ERC-19-0474","article-title":"A xenograft and cell line model of SDH-deficient pheochromocytoma derived from\n                    Sdhb+\/- rats","volume":"27","author":"J F Powers","year":"2020","journal-title":"Endocr Relat Cancer"},{"key":"ref22","doi-asserted-by":"crossref","first-page":"R433","DOI":"10.1530\/ERC-19-0434","article-title":"Advances in paraganglioma-pheochromocytoma cell lines and xenografts","volume":"27","author":"J P Bayley","year":"2020","journal-title":"Endocrine-Related Cancer"},{"key":"ref23","doi-asserted-by":"crossref","first-page":"e0274478","DOI":"10.1371\/journal.pone.0274478","article-title":"Long-term in vitro 2D-culture of SDHB and SDHD-related human paragangliomas and\n                    pheochromocytomas","volume":"17","author":"J P Bayley","year":"2022","journal-title":"PLoS One"},{"key":"ref24","doi-asserted-by":"crossref","first-page":"970","DOI":"10.1038\/nbt.3271","article-title":"Expansion and patterning of cardiovascular progenitors derived from human\n                    pluripotent stem cells","volume":"33","author":"M J Birket","year":"2015","journal-title":"Nat Biotechnol"},{"key":"ref25","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1016\/S1097-2765(00)80367-6","article-title":"Reversible tumorigenesis by MYC in hematopoietic lineages","volume":"4","author":"D W Felsher","year":"1999","journal-title":"Mol Cell"},{"key":"ref26","doi-asserted-by":"crossref","first-page":"5546","DOI":"10.1158\/1078-0432.CCR-12-0977","article-title":"c-Myc and cancer metabolism","volume":"18","author":"D M Miller","year":"2012","journal-title":"Clin Cancer Res"},{"key":"ref27","doi-asserted-by":"crossref","first-page":"9085","DOI":"10.1073\/pnas.0402770101","article-title":"The Fbw7 tumor suppressor regulates glycogen synthase kinase 3\n                    phosphorylation-dependent c-Myc protein degradation","volume":"101","author":"M Welcker","year":"2004","journal-title":"Proc Natl Acad Sci U S A"},{"key":"ref28","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1007\/s12022-019-9575-6","article-title":"A Previously Unrecognized Monocytic Component of Pheochromocytoma and\n                    Paraganglioma","volume":"30","author":"N A Farhat","year":"2019","journal-title":"Endocr Pathol"},{"key":"ref29","first-page":"72","article-title":"A HIF1alpha regulatory loop links hypoxia and mitochondrial signals in\n                    pheochromocytomas","volume":"1","author":"P L Dahia","year":"2005","journal-title":"PLoSGenet"},{"key":"ref30","doi-asserted-by":"crossref","first-page":"38777","DOI":"10.18632\/oncotarget.6091","article-title":"Inactivation of SDH and FH cause loss of 5hmC and increased H3K9me3 in\n                    paraganglioma\/pheochromocytoma and smooth muscle tumors","volume":"6","author":"A S Hoekstra","year":"2015","journal-title":"Oncotarget."}],"container-title":["Experimental and Clinical Endocrinology &amp; Diabetes"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/www.thieme-connect.de\/products\/ejournals\/pdf\/10.1055\/a-2797-3576.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,25]],"date-time":"2026-03-25T23:30:30Z","timestamp":1774481430000},"score":1,"resource":{"primary":{"URL":"http:\/\/www.thieme-connect.de\/DOI\/DOI?10.1055\/a-2797-3576"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,3]]},"references-count":26,"journal-issue":{"issue":"03","published-online":{"date-parts":[[2026,3,25]]},"published-print":{"date-parts":[[2026,3]]}},"URL":"https:\/\/doi.org\/10.1055\/a-2797-3576","archive":["Portico","CLOCKSS"],"relation":{},"ISSN":["0947-7349","1439-3646"],"issn-type":[{"value":"0947-7349","type":"print"},{"value":"1439-3646","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,3]]}}}