Title

Application of multiplex ligation-dependent probe amplification (MLPA) and low pass whole genome sequencing (LP-WGS) to the classification / characterisation of low grade glioneuronal tumours

Document Type

Journal Article

Publication Title

Pathology - Research and Practice

Volume

229

Publisher

Elsevier

School

School of Medical and Health Sciences / Centre for Precision Health

Funders

Royal Perth Hospital Medical Research Foundation, Australia

Comments

Dyke, J., Calapre, L., Beasley, A., Gray, E., Allcock, R., & Bentel, J. (2022). Application of multiplex ligation-dependent probe amplification (MLPA) and low pass whole genome sequencing (LP-WGS) to the classification / characterisation of low grade glioneuronal tumours. Pathology -Research and Practice, 229, article 153724.

https://doi.org/10.1016/j.prp.2021.153724

Abstract

Aims:

Glioneuronal tumours, although rare, are an important cause of treatment-resistant epilepsy. Differential diagnosis of glioneuronal tumour subtypes is complicated by their variable histological appearance and the lack of pathognomonic histological or molecular biomarkers. In this study we have applied techniques available in a diagnostic laboratory setting to characterise molecular and cytogenetic abnormalities in a single institution cohort of glioneuronal tumours.

Methods:

A cohort of 29 glioneuronal tumours that included 21 gangliogliomas and 5 dysembryoplastic neuroepithelial tumours (DNETs) was analysed using low pass whole genome sequencing (WGS) and 2 multiplex ligation-dependent probe amplification (MLPA) central nervous system (CNS) tumour probesets.

Results:

Low pass WGS identified chromosomal or subchromosomal alterations in 15 specimens. The most common chromosomal alterations were gains of chromosome 7 (n = 8) and chromosome 16 (n = 3). The BRAFV600E mutation was detected by MLPA in 9/21 (42.9%) gangliogliomas and 2/2 pleomorphic xanthoastrocytomas (PXAs). Chromosome 7 gains detected by WGS were reflected in MLPAs by overall gains of chromosome 7 gene probes, including those for BRAF, KIAA1549 and EGFR, while an internal BRAF/MKRN1 duplication was detected in a single ganglioglioma. Homozygous CDKN2A/B loss was detected by MLPA in 3 gangliogliomas, with p16 immunohistochemistry supporting these results.

Conclusions:

The combination of low pass WGS and MLPA identifies multiple, diverse genetic and chromosomal alterations in glioneuronal tumours, irrespective of histological tumour grade.

DOI

10.1016/j.prp.2021.153724

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