Genome-wide methylation profiling differentiates benign from aggressive and metastatic pituitary neuroendocrine tumors
(2024) In Acta Neuropathologica 148(1).- Abstract
Aggressive pituitary neuroendocrine tumors (PitNETs)/adenomas are characterized by progressive growth despite surgery and all standard medical therapies and radiotherapy. A subset will metastasize to the brain and/or distant locations and are termed metastatic PitNETs (pituitary carcinomas). Studies of potential prognostic markers have been limited due to the rarity of these tumors. A few recurrent somatic mutations have been identified, and epigenetic alterations and chromosomal rearrangements have not been explored in larger cohorts of aggressive and metastatic PitNETs. In this study, we performed genome-wide methylation analysis, including copy-number variation (CNV) calculations, on tumor tissue specimens from a large international... (More)
Aggressive pituitary neuroendocrine tumors (PitNETs)/adenomas are characterized by progressive growth despite surgery and all standard medical therapies and radiotherapy. A subset will metastasize to the brain and/or distant locations and are termed metastatic PitNETs (pituitary carcinomas). Studies of potential prognostic markers have been limited due to the rarity of these tumors. A few recurrent somatic mutations have been identified, and epigenetic alterations and chromosomal rearrangements have not been explored in larger cohorts of aggressive and metastatic PitNETs. In this study, we performed genome-wide methylation analysis, including copy-number variation (CNV) calculations, on tumor tissue specimens from a large international cohort of 64 patients with aggressive (48) and metastatic (16) pituitary tumors. Twelve patients with non-invasive pituitary tumors (Knosp 0–2) exhibiting an indolent course over a 5 year follow-up served as controls. In an unsupervised hierarchical cluster analysis, aggressive/metastatic PitNETs clustered separately from benign pituitary tumors, and, when only specimens from the first surgery were analyzed, three separate clusters were identified: aggressive, metastatic, and benign PitNETs. Numerous CNV events affecting chromosomal arms and whole chromosomes were frequent in aggressive and metastatic, whereas benign tumors had normal chromosomal copy numbers with only few alterations. Genome-wide methylation analysis revealed different CNV profiles and a clear separation between aggressive/metastatic and benign pituitary tumors, potentially providing biomarkers for identification of these tumors with a worse prognosis at the time of first surgery. The data may refine follow-up routines and contribute to the timely introduction of adjuvant therapy in patients harboring, or at risk of developing, aggressive or metastatic pituitary tumors.
(Less)
- author
- organization
- publishing date
- 2024-12
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- Aggressive pituitary tumor, Methylation analysis, Pituitary adenoma, Pituitary carcinoma, Pituitary neuroendocrine tumor
- in
- Acta Neuropathologica
- volume
- 148
- issue
- 1
- article number
- 68
- publisher
- Springer
- external identifiers
-
- pmid:39580368
- scopus:85209875877
- ISSN
- 0001-6322
- DOI
- 10.1007/s00401-024-02836-5
- language
- English
- LU publication?
- yes
- additional info
- Publisher Copyright: © The Author(s) 2024.
- id
- 1ee55de8-0900-44ca-a933-d37e28cee905
- date added to LUP
- 2025-01-10 09:07:03
- date last changed
- 2025-07-12 00:24:33
@article{1ee55de8-0900-44ca-a933-d37e28cee905,
abstract = {{<p>Aggressive pituitary neuroendocrine tumors (PitNETs)/adenomas are characterized by progressive growth despite surgery and all standard medical therapies and radiotherapy. A subset will metastasize to the brain and/or distant locations and are termed metastatic PitNETs (pituitary carcinomas). Studies of potential prognostic markers have been limited due to the rarity of these tumors. A few recurrent somatic mutations have been identified, and epigenetic alterations and chromosomal rearrangements have not been explored in larger cohorts of aggressive and metastatic PitNETs. In this study, we performed genome-wide methylation analysis, including copy-number variation (CNV) calculations, on tumor tissue specimens from a large international cohort of 64 patients with aggressive (48) and metastatic (16) pituitary tumors. Twelve patients with non-invasive pituitary tumors (Knosp 0–2) exhibiting an indolent course over a 5 year follow-up served as controls. In an unsupervised hierarchical cluster analysis, aggressive/metastatic PitNETs clustered separately from benign pituitary tumors, and, when only specimens from the first surgery were analyzed, three separate clusters were identified: aggressive, metastatic, and benign PitNETs. Numerous CNV events affecting chromosomal arms and whole chromosomes were frequent in aggressive and metastatic, whereas benign tumors had normal chromosomal copy numbers with only few alterations. Genome-wide methylation analysis revealed different CNV profiles and a clear separation between aggressive/metastatic and benign pituitary tumors, potentially providing biomarkers for identification of these tumors with a worse prognosis at the time of first surgery. The data may refine follow-up routines and contribute to the timely introduction of adjuvant therapy in patients harboring, or at risk of developing, aggressive or metastatic pituitary tumors.</p>}},
author = {{Jotanovic, Jelena and Boldt, Henning Bünsow and Burton, Mark and Andersen, Marianne Skovsager and Bengtsson, Daniel and Bontell, Thomas Olsson and Ekman, Bertil and Engström, Britt Edén and Feldt-Rasmussen, Ulla and Heck, Ansgar and Jakovcevic, Antonia and Jørgensen, Jens Otto L. and Kraljevic, Ivana and Kunicki, Jacek and Lindsay, John R. and Losa, Marco and Loughrey, Paul Benjamin and Maiter, Dominique and Maksymowicz, Maria and Manojlovic-Gacic, Emilija and Pahnke, Jens and Petersenn, Stephan and Petersson, Maria and Popovic, Vera and Ragnarsson, Oskar and Rasmussen, Åse Krogh and Reisz, Zita and Saeger, Wolfgang and Schalin-Jäntti, Camilla and Scheie, David and Terreni, Maria Rosa and Tynninen, Olli and Whitelaw, Ben and Burman, Pia and Casar-Borota, Olivera}},
issn = {{0001-6322}},
keywords = {{Aggressive pituitary tumor; Methylation analysis; Pituitary adenoma; Pituitary carcinoma; Pituitary neuroendocrine tumor}},
language = {{eng}},
number = {{1}},
publisher = {{Springer}},
series = {{Acta Neuropathologica}},
title = {{Genome-wide methylation profiling differentiates benign from aggressive and metastatic pituitary neuroendocrine tumors}},
url = {{http://dx.doi.org/10.1007/s00401-024-02836-5}},
doi = {{10.1007/s00401-024-02836-5}},
volume = {{148}},
year = {{2024}},
}