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Mitochondrial DNA mutations in Medulloblastoma

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Mitochondrial DNA mutations in Medulloblastoma. / Funke, Viktoria L E; Sandmann, Sarah; Melcher, Viktoria; Seggewiss, Jochen; Horvath, Judit; Jäger, Natalie; Kool, Marcel; Jones, David T W; Pfister, Stefan M; Milde, Till; Rutkowski, Stefan; Mynarek, Martin; Varghese, Julian; Sträter, Ronald; Rust, Stephan; Seelhöfer, Anja; Reunert, Janine; Fiedler, Barbara; Schüller, Ulrich; Marquardt, Thorsten; Kerl, Kornelius.

In: ACTA NEUROPATHOL COM, Vol. 11, No. 1, 27.07.2023, p. 124.

Research output: SCORING: Contribution to journal › Case report › Research › peer-review

Harvard

Funke, VLE, Sandmann, S, Melcher, V, Seggewiss, J, Horvath, J, Jäger, N, Kool, M, Jones, DTW, Pfister, SM, Milde, T, Rutkowski, S, Mynarek, M, Varghese, J, Sträter, R, Rust, S, Seelhöfer, A, Reunert, J, Fiedler, B, Schüller, U, Marquardt, T & Kerl, K 2023, 'Mitochondrial DNA mutations in Medulloblastoma', ACTA NEUROPATHOL COM, vol. 11, no. 1, pp. 124. https://doi.org/10.1186/s40478-023-01602-0

APA

Funke, V. L. E., Sandmann, S., Melcher, V., Seggewiss, J., Horvath, J., Jäger, N., Kool, M., Jones, D. T. W., Pfister, S. M., Milde, T., Rutkowski, S., Mynarek, M., Varghese, J., Sträter, R., Rust, S., Seelhöfer, A., Reunert, J., Fiedler, B., Schüller, U., ... Kerl, K. (2023). Mitochondrial DNA mutations in Medulloblastoma. ACTA NEUROPATHOL COM, 11(1), 124. https://doi.org/10.1186/s40478-023-01602-0

Vancouver

Funke VLE, Sandmann S, Melcher V, Seggewiss J, Horvath J, Jäger N et al. Mitochondrial DNA mutations in Medulloblastoma. ACTA NEUROPATHOL COM. 2023 Jul 27;11(1):124. https://doi.org/10.1186/s40478-023-01602-0

Bibtex

@article{10557ff0855544a3a860a03ebb2d508c,
title = "Mitochondrial DNA mutations in Medulloblastoma",
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.",
keywords = "Humans, Female, Medulloblastoma/genetics, Mutation/genetics, DNA, Mitochondrial/genetics, Mitochondrial Diseases, Cerebellar Neoplasms/genetics",
author = "Funke, {Viktoria L E} and Sarah Sandmann and Viktoria Melcher and Jochen Seggewiss and Judit Horvath and Natalie J{\"a}ger and Marcel Kool and Jones, {David T W} and Pfister, {Stefan M} and Till Milde and Stefan Rutkowski and Martin Mynarek and Julian Varghese and Ronald Str{\"a}ter and Stephan Rust and Anja Seelh{\"o}fer and Janine Reunert and Barbara Fiedler and Ulrich Sch{\"u}ller and Thorsten Marquardt and Kornelius Kerl",
note = "{\textcopyright} 2023. The Author(s).",
year = "2023",
month = jul,
day = "27",
doi = "10.1186/s40478-023-01602-0",
language = "English",
volume = "11",
pages = "124",
journal = "ACTA NEUROPATHOL COM",
issn = "2051-5960",
publisher = "BioMed Central Ltd.",
number = "1",

}

RIS

TY - JOUR

T1 - Mitochondrial DNA mutations in Medulloblastoma

AU - Funke, Viktoria L E

AU - Sandmann, Sarah

AU - Melcher, Viktoria

AU - Seggewiss, Jochen

AU - Horvath, Judit

AU - Jäger, Natalie

AU - Kool, Marcel

AU - Jones, David T W

AU - Pfister, Stefan M

AU - Milde, Till

AU - Rutkowski, Stefan

AU - Mynarek, Martin

AU - Varghese, Julian

AU - Sträter, Ronald

AU - Rust, Stephan

AU - Seelhöfer, Anja

AU - Reunert, Janine

AU - Fiedler, Barbara

AU - Schüller, Ulrich

AU - Marquardt, Thorsten

AU - Kerl, Kornelius

N1 - © 2023. The Author(s).

PY - 2023/7/27

Y1 - 2023/7/27

N2 - 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.

AB - 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.

KW - Humans

KW - Female

KW - Medulloblastoma/genetics

KW - Mutation/genetics

KW - DNA, Mitochondrial/genetics

KW - Mitochondrial Diseases

KW - Cerebellar Neoplasms/genetics

U2 - 10.1186/s40478-023-01602-0

DO - 10.1186/s40478-023-01602-0

M3 - Case report

C2 - 37501103

VL - 11

SP - 124

JO - ACTA NEUROPATHOL COM

JF - ACTA NEUROPATHOL COM

SN - 2051-5960

IS - 1

ER -