{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T02:53:05Z","timestamp":1783479185722,"version":"3.55.0"},"reference-count":33,"publisher":"National Academy of Sciences","issue":"43","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2010,10,26]]},"abstract":"<jats:p>\n                    Pheochromocytomas are rare neoplasias of neural crest origin arising from chromaffin cells of the adrenal medulla and sympathetic ganglia (extra-adrenal pheochromocytoma). Pheochromocytoma that develop in rats homozygous for a loss-of-function mutation in p27Kip1 (MENX syndrome) show a clear progression from hyperplasia to tumor, offering the possibility to gain insight into tumor pathobiology. We compared the gene-expression signatures of both adrenomedullary hyperplasia and pheochromocytoma with normal rat adrenal medulla. Hyperplasia and tumor show very similar transcriptome profiles, indicating early determination of the tumorigenic signature. Overrepresentation of developmentally regulated neural genes was a feature of the rat lesions. Quantitative RT-PCR validated the up-regulation of 11 genes, including some involved in neural development:\n                    <jats:italic>Cdkn2a<\/jats:italic>\n                    ,\n                    <jats:italic>Cdkn2c<\/jats:italic>\n                    ,\n                    <jats:italic>Neurod1<\/jats:italic>\n                    ,\n                    <jats:italic>Gal<\/jats:italic>\n                    ,\n                    <jats:italic>Bmp7<\/jats:italic>\n                    , and\n                    <jats:italic>Phox2a<\/jats:italic>\n                    . Overexpression of these genes precedes histological changes in affected adrenal glands. Their presence at early stages of tumorigenesis indicates they are not acquired during progression and may be a result of the lack of functional p27Kip1. Adrenal and extra-adrenal pheochromocytoma development clearly follows diverged molecular pathways in MENX rats. To correlate these findings to human pheochromocytoma, we studied nine genes overexpressed in the rat lesions in 46 sporadic and familial human pheochromocytomas. The expression of\n                    <jats:italic>GAL<\/jats:italic>\n                    ,\n                    <jats:italic>DGKH<\/jats:italic>\n                    ,\n                    <jats:italic>BMP7<\/jats:italic>\n                    ,\n                    <jats:italic>PHOX2A<\/jats:italic>\n                    ,\n                    <jats:italic>L1CAM<\/jats:italic>\n                    ,\n                    <jats:italic>TCTE1<\/jats:italic>\n                    ,\n                    <jats:italic>EBF3<\/jats:italic>\n                    ,\n                    <jats:italic>SOX4<\/jats:italic>\n                    , and\n                    <jats:italic>HASH1<\/jats:italic>\n                    was up-regulated, although with different frequencies. Immunohistochemical staining detected high L1CAM expression selectively in 27 human pheochromocytomas but not in 140 nonchromaffin neuroendocrine tumors. These studies reveal clues to the molecular pathways involved in rat and human pheochromocytoma and identify previously unexplored biomarkers for clinical use.\n                  <\/jats:p>","DOI":"10.1073\/pnas.1003956107","type":"journal-article","created":{"date-parts":[[2010,10,11]],"date-time":"2010-10-11T20:53:33Z","timestamp":1286830413000},"page":"18493-18498","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":33,"title":["Pheochromocytoma in rats with multiple endocrine neoplasia (MENX) shares gene expression patterns with human pheochromocytoma"],"prefix":"10.1073","volume":"107","author":[{"given":"Sara","family":"Molatore","sequence":"first","affiliation":[{"name":"Departments of aPathology,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandya","family":"Liyanarachchi","sequence":"additional","affiliation":[{"name":"Human Cancer Genetics Program, Department of Molecular Virology, Immunology, and Medical Genetics, Ohio State University, Columbus, OH 43210;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Irmler","sequence":"additional","affiliation":[{"name":"Experimental Genetics, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aurel","family":"Perren","sequence":"additional","affiliation":[{"name":"Institute of Pathology, University of Bern, 3010 Bern, Switzerland;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Massimo","family":"Mannelli","sequence":"additional","affiliation":[{"name":"Clinical Physiopathology, University of Florence, 50139 Florence, Italy;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tonino","family":"Ercolino","sequence":"additional","affiliation":[{"name":"Clinical Physiopathology, University of Florence, 50139 Florence, Italy;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Felix","family":"Beuschlein","sequence":"additional","affiliation":[{"name":"Endocrine Research Unit, Medizinische Klinik-Innenstadt, Ludwig-Maximilians-University, 80336 Munich, Germany;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barbara","family":"Jarzab","sequence":"additional","affiliation":[{"name":"Department of Nuclear Medicine, Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, 44-100, Gliwice, Poland;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan","family":"Wloch","sequence":"additional","affiliation":[{"name":"Department of Nuclear Medicine, Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, 44-100, Gliwice, Poland;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacek","family":"Ziaja","sequence":"additional","affiliation":[{"name":"Department of General, Vascular, and Transplant Surgery, Silesian Medical University, 40-027, Katowice, Poland;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saida","family":"Zoubaa","sequence":"additional","affiliation":[{"name":"Departments of aPathology,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frauke","family":"Neff","sequence":"additional","affiliation":[{"name":"Departments of aPathology,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johannes","family":"Beckers","sequence":"additional","affiliation":[{"name":"Experimental Genetics, and"},{"name":"Technical University Munich, Center of Life and Food Sciences Weihenstephan, 85354 Freising, Germany; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heinz","family":"H\u00f6fler","sequence":"additional","affiliation":[{"name":"Departments of aPathology,"},{"name":"Institute of Pathology, Technical University Munich, 81675 Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael J.","family":"Atkinson","sequence":"additional","affiliation":[{"name":"Radiation Biology, Helmholtz Zentrum M\u00fcnchen, 85764 Neuherberg, Germany;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natalia S.","family":"Pellegata","sequence":"additional","affiliation":[{"name":"Departments of aPathology,"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2010,10,11]]},"reference":[{"key":"e_1_3_4_1_2","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1097\/01.cco.0000198017.45982.06","article-title":"Evolving concepts in pheochromocytoma and paraganglioma","volume":"18","author":"Dahia PL","year":"2006","unstructured":"PL Dahia, Evolving concepts in pheochromocytoma and paraganglioma. 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