Corticotroph Aggressive Pituitary Tumors and Carcinomas Frequently Harbor ATRX Mutations
| العنوان: | Corticotroph Aggressive Pituitary Tumors and Carcinomas Frequently Harbor ATRX Mutations |
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| المؤلفون: | Casar-Borota, Olivera, Boldt, Henning Bünsow, Engström, Britt Edén, Andersen, Marianne Skovsager, Baussart, Bertrand, Bengtsson, Daniel, Berinder, Katarina, Ekman, Bertil, 1958, Feldt-Rasmussen, Ulla, Höybye, Charlotte, Jörgensen, Jens Otto L., Kolnes, Anders Jensen, Korbonits, Marta, Rasmussen, Åse Krogh, Lindsay, John R., Loughrey, Paul Benjamin, Maiter, Dominique, Manojlovic-Gacic, Emilija, Pahnke, Jens, Poliani, Pietro Luigi, Popovic, Vera, Ragnarsson, Oskar, Schalin-Jantti, Camilla, Scheie, David, Toth, Miklos, Villa, Chiara, Wirenfeldt, Martin, Kunicki, Jacek, Burman, Pia |
| المصدر: | Journal of Clinical Endocrinology and Metabolism. 106(4):1183-1194 |
| مصطلحات موضوعية: | ATRX (alpha thalassemia/mental retardation syndrome X-linked), aggressive PitNETs, pituitary carcinoma, pituitary adenoma, Cushings disease |
| الوصف: | Context: Aggressive pituitary tumors (APTs) are characterized by unusually rapid growth and lack of response to standard treatment. About 1% to 2% develop metastases being classified as pituitary carcinomas (PCs). For unknown reasons, the corticotroph tumors are overrepresented among APTs and PCs. Mutations in the alpha thalassemia/mental retardation syndrome X-linked (ATRX) gene, regulating chromatin remodeling and telomere maintenance, have been implicated in the development of several cancer types, including neuroendocrine tumors. Objective: To study ATRX protein expression and mutational status of the ATRX gene in APTs and PCs. Design: We investigated ATRX protein expression by using immunohistochemistry in 30 APTs and 18 PCs, mostly of Pit-1 and T-Pit cell lineage. In tumors lacking ATRX immunolabeling, mutational status of the ATRX gene was explored. Results: Nine of the 48 tumors (19%) demonstrated lack of ATRX immunolabelling with a higher proportion in patients with PCs (5/18; 28%) than in those with APTs (4/30;13%). Lack of ATRX was most common in the corticotroph tumors, 7/22 (32%), versus tumors of the Pit-1 lineage, 2/24 (8%). Loss-of-function ATRX mutations were found in all 9 ATRX immunonegative cases: nonsense mutations (n = 4), frameshift deletions (n = 4), and large deletions affecting 22-28 of the 36 exons (n = 3). More than 1 ATRX gene defect was identified in 2 PCs. Conclusion: ATRX mutations occur in a subset of APTs and are more common in corticotroph tumors. The findings provide a rationale for performing ATRX immunohistochemistry to identify patients at risk of developing aggressive and potentially metastatic pituitary tumors. |
| وصف الملف: | electronic |
| URL الوصول: | https://urn.kb.se/resolve?urn=urn:nbn:se:liu:diva-176196 https://liu.diva-portal.org/smash/get/diva2:1562988/FULLTEXT01.pdf |
| قاعدة البيانات: | SwePub |
| تدمد: | 0021972X 19457197 |
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| DOI: | 10.1210/clinem/dgaa749 |