The chromatin guardian ATRX is a strong prognostic biomarker in melanoma

In our study, we investigated the role of the chromatin remodeler ATRX in the progression of cutaneous melanoma. We analyzed ATRX protein expression in over 350 melanomas, correlating findings with clinical data, tumor proliferation rates, and vessel density. Additionally, we examined whole-genome sequencing data from 70 melanoma metastases to assess ATRX genetic alterations and compared these with protein expression patterns. We observed a significant reduction in ATRX protein expression in metastases compared to primary tumors: 51% of primary melanomas showed ATRX positivity in over 50% of tumor cells, versus only 25% of metastases (p = 0.01). ATRX loss was associated with earlier metastasis (median 17 vs. 46 months), reduced overall survival (median 69 vs. 162.5 months), and worse tumor-specific survival (p = 0.01). ATRX expression correlated positively with vessel density (rs = 0.3) and negatively with proliferation (rs = – 0.3), suggesting a role in hypoxia response. Genetically, intronic mutations were most frequent (80%), followed by copy number variations (loss: 29%, gain: 37%). Interestingly, ATRX copy number changes did not correlate with protein levels, pointing to epigenetic regulation. Our findings highlight ATRX loss as an early and prognostically relevant event in melanoma, with potential as a therapeutic target.

Authors

Institutions

Publication Details

Journal
Scientific Reports
Published
2025-12-18
DOI
https://doi.org/10.1038/s41598-025-30842-4
Primary Topic
Chromatin Remodeling and Cancer
Type
article
Field-Weighted Citation Impact
0.00

Funders

Controls
|||
ALL TIME
JAN
FEB
MAR
APR
MAY
JUN
JUL
AUG
SEP
OCT
article

The chromatin guardian ATRX is a strong prognostic biomarker in melanoma

Rebekka Wegmann, René Holtackers, Viktor Hendrik Koelzer, Faisal Alquaddoomi et al.
Scientific Reports
Chromatin Remodeling and Cancer
article

The chromatin guardian ATRX is a strong prognostic biomarker in melanoma

Rebekka Wegmann, René Holtackers, Viktor Hendrik Koelzer, Faisal Alquaddoomi, Laurie Prélot, Marina Bacac, Jonas Albinus, Audrey van Drogen, María Lourdes Rosano-González, André Fedier, Marina Tusup, Marcus Vetter, Sujana Sivapatham, Franziska Singer, Stefanie Engler, Ricardo Coelho, Markus Gabriel Manz, Patrick G. A. Pedrioli, Bernd Bodenmiller, Lars Bosshard, Andreas N. WICKI, Linda Grob, Natalia Chicherova, Daniel Baumhoer, Michael Weller, Tobias Schär, Beatrice Beck‐Schimmer, Gabriela Senti, Stefan Nicolet, Petra Catalina Schwalie, Christian P. Kunze, Kjong-Van Lehmann, Martin Mehnert, Fabian Wendt, Cinzia Esposito, Sonali Andani, Lara Bernasconi, Holger Moch, Flavio C. Lombardo, Miriam Wanner, Katja Eschbach, Lucas Pelkmans, Martin Erkens, Severin Schwan, Gregor Zuend, Alice K. Jacobs, Vipin T. Sreedharan, Shuqing Yu, Abdullah Kahraman, Detlef Günther, Melike Ak, Nicola Miglino, Christopher R. Frei, Gunnar Rätsch, Niko Beerenwinkel, Michael Prummer, Sandra Goetze, Stefan G. Stark, Jack Kuipers, Tatjana Vlajnic, Esther Danenberg, Ruben Casanova, Cassandra Litchfield, Francis Jacob, Per-Olof Attinger, Reinhard Dummer, Pedro Ferreira, Tamara Huesser, Berend Snijder, Anja Frei, Julian M. Metzler, Bruno S. Frey, Gabriele Gut, Ximena Bonilla, Wenguang Shao, Salvatore Piscuoglio, Ilaria Alborelli, Simone E. Muenst, Mattheus H. E. Wildschut, Mónica Núñez López, Norbert Wey, Christian Beisel, Johanna Ziegler, Tinu M. Thomas, Viola A Heinzelmann-Schwarz, Rudolf Aebersold, Ramona Schlenker, Charlotte K.Y. Ng, Daniela Mihic‐Probst, Anne Bertolini, Christian Rommel, Martin Zoche, Maya D’Costa, Alva Rani James, Ulrike Lischetti, Anja Irmisch, Werner Kuebler, Stéphane Chevrier, André Kahles, Bernd Wollscheid, Mustafa A. Tuncel, Philip M. Jermann, Sandra Weber, Emanuela S. Milani, Natascha Santacroce, Julien Mena, Markus Tolnay, Natalie R. Davidson, Pirmin Haeuptle, Nora C. Toussaint, Vinko Toševski, Jacobo Sarabia del Castillo, William P. Weber, Fabiola Prutek, Sebastian Lugert, Tanmay Tanna, Daniel J. Stekhoven, Natalie Rimmer, Monica-Andreea Baciu-Drăgan, Alexandre Theocharides, Philipp Markolin, Christian Kurzeder, André Fitsche, Byron Calgua, Joanna Ficek-Pascual, Marta Nowak, Mitchell P. Levesque, Riccardo Murri, Alexander Immer, Gerd Maass, Marc Zimmermann, Tim M. Jaeger, Mathilde Ritter, Silvana I. Albert, Alanna Mihic, Fabius Wiesmann
article en

Abstract

In our study, we investigated the role of the chromatin remodeler ATRX in the progression of cutaneous melanoma. We analyzed ATRX protein expression in over 350 melanomas, correlating findings with clinical data, tumor proliferation rates, and vessel density. Additionally, we examined whole-genome sequencing data from 70 melanoma metastases to assess ATRX genetic alterations and compared these with protein expression patterns. We observed a significant reduction in ATRX protein expression in metastases compared to primary tumors: 51% of primary melanomas showed ATRX positivity in over 50% of tumor cells, versus only 25% of metastases (p = 0.01). ATRX loss was associated with earlier metastasis (median 17 vs. 46 months), reduced overall survival (median 69 vs. 162.5 months), and worse tumor-specific survival (p = 0.01). ATRX expression correlated positively with vessel density (rs = 0.3) and negatively with proliferation (rs = – 0.3), suggesting a role in hypoxia response. Genetically, intronic mutations were most frequent (80%), followed by copy number variations (loss: 29%, gain: 37%). Interestingly, ATRX copy number changes did not correlate with protein levels, pointing to epigenetic regulation. Our findings highlight ATRX loss as an early and prognostically relevant event in melanoma, with potential as a therapeutic target.

Scientific ReportsVol. 16(1)
Roche (Switzerland) (CH), University of Bern (CH), SIB Swiss Institute of Bioinformatics (CH), Bern University of Applied Sciences (CH), University of Basel (CH), ZHAW Zurich University of Applied Sciences (CH), University of Zurich (CH), University Hospital of Basel (CH), FHNW University of Applied Sciences and Arts Northwestern Switzerland (CH), ETH Zurich (CH), Roche Pharma AG (Germany) (DE), Integrated Oncology (United States) (US), Health and Safety Authority (IE), University Hospital of Zurich (CH), Psychiatry Baselland (CH), Life Science Zurich (CH), Veterinary Anaesthesia Services (Switzerland) (CH), Swiss Data Science Center (CH), University Hospital Cologne (DE), RWTH Aachen University (DE), FH Aachen (DE)
Oncosuisse
Openalex Percentile: Top 63%
Chromatin Remodeling and Cancer
DOIOpen Access PDFOpenAlex
AI Navigator

Ask Laika to Summarize, Analyze, and Connect papers live on the map.

Summarize Papers & Methodologies

Extract key findings, datasets, and comparative methods across publications.

Benchmark Rankings & Visual Analytics

Rank top research institutions, authors, funders, topics, and journals by Field-Weighted Citation Impact (FWCI) and paper volume with instant charts.

Connect Distant Disciplines

Bridge topological clusters on the map to find hidden collaborative intersections.