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Pia Burman


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Corticotroph Aggressive Pituitary Tumors and Carcinomas Frequently Harbor ATRX Mutations


  • Olivera Casar-Borota
  • Henninǵbünsow Boldt
  • Brittédén Engström
  • Marianne Skovsager Andersen
  • Bertrand Baussart
  • Daniel Bengtsson
  • Katarina Berinder
  • Bertil Ekman
  • Ulla Feldt-Rasmussen
  • Charlotte Höybye
  • Jens Otto L. Jørgensen
  • Anders Jensen Kolnes
  • Márta Korbonits
  • Åse Krogh Rasmussen
  • John R. Lindsay
  • Paul Benjamin Loughrey
  • Dominique Maiter
  • Emilija Manojlovic-Gacic
  • Jens Pahnke
  • Pietro Luigi Poliani
  • Vera Popovic
  • Oskar Ragnarsson
  • Camilla Schalin-Jäntti
  • David Scheie
  • Miklós Tóth
  • Chiara Villa
  • Martin Wirenfeldt
  • Jacek Kunicki
  • Pia Burman

Summary, in English

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.


  • Genomics, Diabetes and Endocrinology
  • EXODIAB: Excellence of Diabetes Research in Sweden

Publishing year







Journal of Clinical Endocrinology and Metabolism





Document type

Journal article


Oxford University Press


  • Cancer and Oncology


  • aggressive PitNETs
  • ATRX (alpha thalassemia/mental retardation syndrome X-linked)
  • Cushing's disease
  • pituitary adenoma
  • pituitary carcinoma



Research group

  • Genomics, Diabetes and Endocrinology


  • ISSN: 0021-972X