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Neurooncol Adv
Neurooncol Adv
noa
Neuro-Oncology Advances
2632-2498
Oxford University Press US

10.1093/noajnl/vdae090.004
vdae090.004
Final Category: Basic Science Brain Metastases
AcademicSubjects/MED00300
AcademicSubjects/MED00310
BSBM-04 THE MULTI-OMIC LANDSCAPE OF SOMATIC VARIATION ACROSS A PAN-CANCER COHORT OF BRAIN METASTASES
Hall Grace University of Melbourne, Parkville, Australia
Melbourne Bioinformatics, Parkville, Australia

Campbell Bethany Department of Surgery, University of Melbourne, Parkville, Australia

Stylli Stanley Department of Surgery, University of Melbourne, Parkville, Australia
Royal Melbourne Hospital, Parkville, Australia

Jung Chol-Hee Melbourne Bioinformatics, Parkville, Australia

Pope Bernard Department of Surgery, University of Melbourne, Parkville, Australia
Melbourne Bioinformatics, Parkville, Australia

Park Daniel Melbourne Bioinformatics, Parkville, Australia

Molania Ramyar Walter and Eliza Hall Institute, Parkville, Australia

Bedo Justin Walter and Eliza Hall Institute, Parkville, Australia

Ureta Jennifer Walter and Eliza Hall Institute, Parkville, Australia

Rodrigues Silvia Department of Pathology, Weill Cornell Medicine, NY, USA

Fidalgo-Ribeiro Caroline Department of Pathology, Weill Cornell Medicine, NY, USA

Loda Massimo Department of Pathology, Weill Cornell Medicine, NY, USA

McCoy Patrick Royal Melbourne Hospital, Parkville, Australia

Gray Clint Gillies McIndoe Research Institute, Wellington, New Zealand

Tan Swee Gillies McIndoe Research Institute, Wellington, New Zealand
Department of Surgery, University of Melbourne, Parkville, Australia

Wickremesekera Agadha Wellington Regional Hospital, Wellington, New Zealand
Department of Surgery, University of Melbourne, Parkville, Australia

Saunders Christobel Department of Surgery, University of Melbourne, Parkville, Australia
Royal Melbourne Hospital, Parkville, Australia

Drummond Kate Department of Neurosurgery, Royal Melbourne Hospital, Parkville, Australia
Department of Surgery, University of Melbourne, Parkville, Australia

Corcoran Niall Department of Surgery, University of Melbourne, Parkville, Australia
Royal Melbourne Hospital, Parkville, Australia

Dimou James Department of Surgery, University of Melbourne, Parkville, Australia
Department of Neurosurgery, Royal Melbourne Hospital, Parkville, Australia

Papenfuss Tony Walter and Eliza Hall Institute, Parkville, Australia

Hovens Christopher Department of Surgery, University of Melbourne, Parkville, Australia
Royal Melbourne Hospital, Parkville, Australia

8 2024
02 8 2024
02 8 2024
6 Suppl 1 2024 SNO/ASCO CNS Metastases Conference i2i2
© The Author(s) 2024. Published by Oxford University Press, the Society for Neuro-Oncology and the European Association of Neuro-Oncology.
2024
https://creativecommons.org/licenses/by-nc/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (https://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com

Abstract

INTRODUCTION

Brain metastases pose a significant and growing challenge in clinical practice, yet the molecular variants of this tumor type has not previously been examined comprehensively across multiple cancer types. In particular, there has been limited focus on contrasting the genetic profiles of common brain metastases originating from primary sites like lung, breast, melanoma, colorectal, and renal cancers, with those arising infrequently such as prostate and others.

METHODS

We have prospectively collected over 125 fresh frozen brain metastases and matching germline reference samples from 14 different primary tumor types and to date have performed WGS, RNA-Seq and Epic 850k methylation profiling on 60 of these samples spanning both common and rare brain metastases. We have employed machine learning algorithms, network analysis techniques, and integrative bioinformatics pipelines to extract meaningful insights into the biological underpinnings of brain metastasis formation.

RESULTS

We conducted an in-depth investigation into the genomic, transcriptomic, and epigenomic profiles of brain metastases, spanning both common and rare types. By merging these diverse datasets, we identified distinct molecular modifications linked to brain metastases with low incidence rates compared to those more frequently observed. Notably, we observed heightened alterations in the regulation of Golgi dynamics, sensing of lipid species, chromatin remodeling factors, and cytoskeletal remodeling in rare brain metastases. These changes likely influence cell migration and invasion dynamics, elucidating the potential for unique characteristics of less common brain metastasis types.

CONCLUSIONS

This research indicates that the molecular mechanisms driving the formation of brain metastases may vary depending on whether the primary malignancy frequently or infrequently spreads to the brain. Studies such as these, will aid in eventually driving innovations in precision oncology and ultimately improving patient outcomes.
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