Corticotroph Aggressive Pituitary Tumors and Carcinomas Frequently Harbor ATRX Mutations

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Casar-Borota , O , Boldt , H B , Engstrom , B E , Andersen , M S , Baussart , B , Bengtsson , D , Berinder , K , Ekman , B , Feldt-Rasmussen , U , Hoybye , C , Jorgensen , J O L , Kolnes , A J , Korbonits , M , Rasmussen , A K , Lindsay , J R , Loughrey , P B , Maiter , D , Manojlovic-Gacic , E , Pahnke , J , Poliani , P L , Popovic , V , Ragnarsson , O , Schalin-Jäntti , C , Scheie , D , Toth , M , Villa , C , Wirenfeldt , M , Kunicki , J & Burman , P 2021 , ' Corticotroph Aggressive Pituitary Tumors and Carcinomas Frequently Harbor ATRX Mutations ' , Journal of Clinical Endocrinology and Metabolism , vol. 106 , no. 4 , pp. 1183-1194 .

Title: Corticotroph Aggressive Pituitary Tumors and Carcinomas Frequently Harbor ATRX Mutations
Author: Casar-Borota, Olivera; Boldt, Henning Bünsow; Engstrom, Britt Eden; Andersen, Marianne Skovsager; Baussart, Bertrand; Bengtsson, Daniel; Berinder, Katarina; Ekman, Bertil; Feldt-Rasmussen, Ulla; Hoybye, Charlotte; Jorgensen, Jens Otto L.; Kolnes, Anders Jensen; Korbonits, Marta; Rasmussen, Ase Krogh; Lindsay, John R.; Loughrey, Paul Benjamin; Maiter, Dominique; Manojlovic-Gacic, Emilija; Pahnke, Jens; Poliani, Pietro Luigi; Popovic, Vera; Ragnarsson, Oskar; Schalin-Jäntti, Camilla; Scheie, David; Toth, Miklos; Villa, Chiara; Wirenfeldt, Martin; Kunicki, Jacek; Burman, Pia
Contributor organization: HUS Abdominal Center
University of Helsinki
Endokrinologian yksikkö
Date: 2021-04
Language: eng
Number of pages: 12
Belongs to series: Journal of Clinical Endocrinology and Metabolism
ISSN: 0021-972X
Abstract: 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.
Subject: ATRX (alpha thalassemia/mental retardation syndrome X-linked)
aggressive PitNETs
pituitary carcinoma
pituitary adenoma
Cushing's disease
3121 General medicine, internal medicine and other clinical medicine
3122 Cancers
Peer reviewed: Yes
Rights: cc_by
Usage restriction: openAccess
Self-archived version: publishedVersion

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