Corticotroph Aggressive Pituitary Tumors and Carcinomas Frequently Harbor ATRX Mutations
(2021) In Journal of Clinical Endocrinology and Metabolism 106(4). p.1183-1194- 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,... (More)
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.
(Less)
- author
- organization
- publishing date
- 2021-04-01
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- aggressive PitNETs, ATRX (alpha thalassemia/mental retardation syndrome X-linked), Cushing's disease, pituitary adenoma, pituitary carcinoma
- in
- Journal of Clinical Endocrinology and Metabolism
- volume
- 106
- issue
- 4
- pages
- 12 pages
- publisher
- Oxford University Press
- external identifiers
-
- pmid:33106857
- scopus:85100467499
- ISSN
- 0021-972X
- DOI
- 10.1210/clinem/dgaa749
- language
- English
- LU publication?
- yes
- id
- 4ee7be79-2f34-4156-a052-86e8d69cf9f1
- date added to LUP
- 2022-03-08 13:50:20
- date last changed
- 2025-03-18 16:11:15
@article{4ee7be79-2f34-4156-a052-86e8d69cf9f1,
abstract = {{<p>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.</p>}},
author = {{Casar-Borota, Olivera and Boldt, Henninǵbünsow and Engström, Brittédén and Andersen, Marianne Skovsager and Baussart, Bertrand and Bengtsson, Daniel and Berinder, Katarina and Ekman, Bertil and Feldt-Rasmussen, Ulla and Höybye, Charlotte and Jørgensen, Jens Otto L. and Kolnes, Anders Jensen and Korbonits, Márta and Rasmussen, Åse Krogh and Lindsay, John R. and Loughrey, Paul Benjamin and Maiter, Dominique and Manojlovic-Gacic, Emilija and Pahnke, Jens and Poliani, Pietro Luigi and Popovic, Vera and Ragnarsson, Oskar and Schalin-Jäntti, Camilla and Scheie, David and Tóth, Miklós and Villa, Chiara and Wirenfeldt, Martin and Kunicki, Jacek and Burman, Pia}},
issn = {{0021-972X}},
keywords = {{aggressive PitNETs; ATRX (alpha thalassemia/mental retardation syndrome X-linked); Cushing's disease; pituitary adenoma; pituitary carcinoma}},
language = {{eng}},
month = {{04}},
number = {{4}},
pages = {{1183--1194}},
publisher = {{Oxford University Press}},
series = {{Journal of Clinical Endocrinology and Metabolism}},
title = {{Corticotroph Aggressive Pituitary Tumors and Carcinomas Frequently Harbor ATRX Mutations}},
url = {{http://dx.doi.org/10.1210/clinem/dgaa749}},
doi = {{10.1210/clinem/dgaa749}},
volume = {{106}},
year = {{2021}},
}