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Mitochondrial DNA mutations in Medulloblastoma

Authors :
Viktoria L. E. Funke
Sarah Sandmann
Viktoria Melcher
Jochen Seggewiss
Judit Horvath
Natalie Jäger
Marcel Kool
David T. W. Jones
Stefan M. Pfister
Till Milde
Stefan Rutkowski
Martin Mynarek
Julian Varghese
Ronald Sträter
Stephan Rust
Anja Seelhöfer
Janine Reunert
Barbara Fiedler
Ulrich Schüller
Thorsten Marquardt
Kornelius Kerl
Source :
Acta Neuropathologica Communications, Vol 11, Iss 1, Pp 1-4 (2023)
Publication Year :
2023
Publisher :
BMC, 2023.

Abstract

Abstract To date, several studies on genomic events underlying medulloblastoma (MB) biology have expanded our understanding of this tumour entity and led to its division into four groups—WNT, SHH, group 3 (G3) and group 4 (G4). However, there is little information about the relevance of pathogenic mitochondrial DNA (mtDNA) mutations and their consequences across these. In this report, we describe the case of a female patient with MB and a mitochondriopathy, followed by a study of mtDNA variants in MB groups. After being diagnosed with G4 MB, the index patient was treated in line with the HIT 2000 protocol with no indications of relapse after five years. Long-term side effects of treatment were complemented by additional neurological symptoms and elevated lactate levels ten years later, resulting in suspected mitochondrial disease. This was confirmed by identifying a mutation in the MT-TS1 gene which appeared homoplasmic in patient tissue and heteroplasmic in the patient’s mother. Motivated by this case, we explored mtDNA mutations across 444 patients from ICGC and HIT cohorts. While there was no statistically significant enrichment of mutations in one MB group, both cohorts encompassed a small group of patients harbouring potentially deleterious mtDNA variants. The case presented here highlights the possible similarities between sequelae caused by MB treatment and neurological symptoms of mitochondrial dysfunction, which may apply to patients across all MB groups. In the context of the current advances in characterising and interpreting mtDNA aberrations, recognising affected patients could enhance our future knowledge regarding the mutations’ impact on carcinogenesis and cancer treatment.

Details

Language :
English
ISSN :
20515960
Volume :
11
Issue :
1
Database :
Directory of Open Access Journals
Journal :
Acta Neuropathologica Communications
Publication Type :
Academic Journal
Accession number :
edsdoj.4d42ac6cc3f343f1a26382b1265c71a1
Document Type :
article
Full Text :
https://doi.org/10.1186/s40478-023-01602-0