Prognostic and predictive biomarkers in central nervous system tumours: the molecular state of play

Laveniya Satgunaseelan; Joanne Sy; Brindha Shivalingam; Hao-Wen Sim; Kimberley L Alexander; Michael E Buckland

doi:10.1016/j.pathol.2023.11.003

Prognostic and predictive biomarkers in central nervous system tumours: the molecular state of play

Pathology. 2024 Mar;56(2):158-169. doi: 10.1016/j.pathol.2023.11.003. Epub 2023 Dec 12.

Authors

Laveniya Satgunaseelan¹, Joanne Sy², Brindha Shivalingam³, Hao-Wen Sim⁴, Kimberley L Alexander⁵, Michael E Buckland⁶

Affiliations

¹ Department of Neuropathology, Royal Prince Alfred Hospital, Sydney, NSW, Australia; Sydney Medical School, Faculty of Medicine and Health Sciences, The University of Sydney, Sydney, NSW, Australia; Department of Neurosurgery, Chris O'Brien Lifehouse, Sydney, NSW, Australia.
² Department of Neuropathology, Royal Prince Alfred Hospital, Sydney, NSW, Australia; Sydney Medical School, Faculty of Medicine and Health Sciences, The University of Sydney, Sydney, NSW, Australia.
³ Sydney Medical School, Faculty of Medicine and Health Sciences, The University of Sydney, Sydney, NSW, Australia; Department of Neurosurgery, Chris O'Brien Lifehouse, Sydney, NSW, Australia.
⁴ Sydney Medical School, Faculty of Medicine and Health Sciences, The University of Sydney, Sydney, NSW, Australia; Department of Medical Oncology, Chris O'Brien Lifehouse, Sydney, NSW, Australia; Faculty of Medicine and Health, University of New South Wales, Sydney, NSW, Australia.
⁵ Department of Neuropathology, Royal Prince Alfred Hospital, Sydney, NSW, Australia; Department of Neurosurgery, Chris O'Brien Lifehouse, Sydney, NSW, Australia; School of Medical Sciences, Faculty of Medicine and Health, The University of Sydney, Sydney, NSW, Australia.
⁶ Department of Neuropathology, Royal Prince Alfred Hospital, Sydney, NSW, Australia; Sydney Medical School, Faculty of Medicine and Health Sciences, The University of Sydney, Sydney, NSW, Australia. Electronic address: Michael.Buckland@sydney.edu.au.

PMID: 38233331
DOI: 10.1016/j.pathol.2023.11.003

Abstract

Central nervous system (CNS) tumours were one of the first cancer types to adopt and integrate molecular profiling into routine clinical diagnosis in 2016. The vast majority of these biomarkers, used to discriminate between tumour types, also offered prognostic information. With the advent of The Cancer Genome Atlas (TCGA) and other large genomic datasets, further prognostic sub-stratification was possible within tumour types, leading to increased precision in CNS tumour grading. This review outlines the evolution of the molecular landscape of adult CNS tumours, through the prism of World Health Organization (WHO) Classifications. We begin our journey in the pre-molecular era, where high-grade gliomas were divided into 'primary' and 'secondary' glioblastomas. Molecular alterations explaining these clinicopathological observations were the first branching points of glioma diagnostics, with the discovery of IDH1/2 mutations and 1p/19q codeletion. Subsequently, the rigorous characterisation of paediatric gliomas led to the unearthing of histone H3 alterations as a key event in gliomagenesis, which also had implications for young adult patients. Simultaneously, studies investigating prognostic biomarkers within tumour types were undertaken. Certain genomic phenotypes were found to portend unfavourable outcomes, for example, MYCN amplification in spinal ependymoma. The arrival of methylation profiling, having revolutionised the diagnosis of CNS tumours, now promises to bring increased prognostic accuracy, as has been shown in meningiomas. While MGMT promoter hypermethylation has remained a reliable biomarker of response to cytotoxic chemotherapy, targeted therapy in CNS tumours has unfortunately not had the success of other cancers. Therefore, predictive biomarkers have lagged behind the identification of prognostic biomarkers in CNS tumours. Emerging research from new clinical trials is cause for guarded optimism and may shift our conceptualisation of predictive biomarker testing in CNS tumours.

Keywords: Central nervous system; biomarker; ependymoma; glioblastoma; glioma; meningioma; predictive; prognosis.

Publication types

Review

MeSH terms

Biomarkers
Biomarkers, Tumor / genetics
Brain Neoplasms* / diagnosis
Brain Neoplasms* / genetics
Brain Neoplasms* / therapy
Central Nervous System Neoplasms* / diagnosis
Central Nervous System Neoplasms* / genetics
Child
Glioma* / diagnosis
Glioma* / genetics
Humans
Isocitrate Dehydrogenase / genetics
Mutation
Prognosis
Young Adult

Substances

Biomarkers
Isocitrate Dehydrogenase
Biomarkers, Tumor