# A microdeletion event at 19q13.43 in IDH-mutant astrocytomas is strongly correlated with MYC overexpression

## TL;DR

A small deletion on chromosome 19 is linked to increased MYC activity in certain brain tumors, suggesting a new way these tumors develop.

## Contribution

Identifies a novel 19q13.43 microdeletion mechanism associated with MYC overexpression in IDH-mutant astrocytomas.

## Key findings

- 86 out of 236 astrocytomas lacked proximal MYC network alterations but showed MYC overexpression.
- A 19q13.43 microdeletion involving 15 genes was found to inversely correlate with MYC expression.
- Microdeletion cases showed intermediate genomic instability compared to other tumor types.

## Abstract

MYC dysregulation is pivotal in the onset and progression of IDH-mutant gliomas, mostly driven by copy-number alterations, regulatory element alterations, or epigenetic changes. Our pilot analysis uncovered instances of relative MYC overexpression without alterations in the proximal MYC network (PMN), prompting a deeper investigation into potential novel oncogenic mechanisms. Analysing comprehensive genomics profiles of 236 “IDH-mutant 1p/19q non-co-deleted” lower-grade gliomas from The Cancer Genome Atlas, we identified somatic genomic alterations within the PMN. In tumours without PMN-alterations but with MYC-overexpression, genes correlated with MYC-overexpression were identified. Our analyses yielded that 86/236 of astrocytomas exhibited no PMN-alterations, a subset of 21/86 displaying relative MYC overexpression. Within this subset, we discovered 42 genes inversely correlated with relative MYC expression, all on 19q. Further analysis pinpointed a minimal common region at 19q13.43, encompassing 15 genes. The inverse correlations of these 15 genes with relative MYC overexpression were re-confirmed using independent scRNAseq data. Further, the micro-deleted astrocytoma subset displayed significantly higher genomic instability compared to WT cases, but lower instability compared to PMN-hit cases. This newly identified 19q micro-deletion represents a potential novel mechanism underlying MYC dysregulation in astrocytomas. Given the prominence of 19q loss in IDH-mutant gliomas, our findings bear significant implications for understanding gliomagenesis.

The online version contains supplementary material available at 10.1186/s40478-024-01811-1.