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\begin{document}

\title{Rare Cases of Medulloblastoma with Hypermutation}



\author[1]{Aditi Bagchi}%
\author[2]{Ian Beddows}%
\author[3]{Albert Cornelius}%
\author[4]{Giles Robinson}%
\author[2]{Scott Jewell}%
\affil[1]{St Jude Children's Research Hospital}%
\affil[2]{Van Andel Research Institute}%
\affil[3]{Helen DeVos Children's Hospital}%
\affil[4]{St. Jude}%


\vspace{-1em}



  
  \date{June 12, 2024}


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\selectlanguage{english}
\begin{abstract}
Medulloblastoma (MB) is the most common malignant brain tumor of
childhood and is reported to have a low mutational burden. However, in
this study, we identified nine MBs with high mutational burden by next
generation sequencing. Of them, two had canonical mutations in the POLE
proof-reading domain, where a large proportion of mutations in these
tumor genomes contributed to signature 10. We report very rare
incidences of hypermutation in MB and mechanisms driving mutagenesis.
Strikingly, of the four known molecular subgroups in MB----SHH, WNT,
Group 3, and Group 4---both the POLE-mutated MBs belonged to the SHH
subgroup.%
\end{abstract}%



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\textbf{Rare Cases of Medulloblastoma with Hypermutation}

Aditi Bagchi, St. Jude Children's Research Hospital, Van Andel Institute
Graduate School, and Spectrum Health Helen DeVos Children's Hospital;
Ian Beddows, Van Andel Research Institute, Bioinformatics and
Biostatistics Core; Albert Cornelius, Spectrum Health Helen DeVos
Children's Hospital; Giles W Robinson, St. Jude Children's Hospital
Research Hospital; and Scott D. Jewell, Van Andel Research Institute,
Pathology and Biorepository Core

\textbf{Co-Corresponding Authors:}

Scott D. Jewell, Van Andel Institute, 333 Bostwick Avenue NE, Grand
Rapids, MI 49503; Tel: 616-232-5435; email

\emph{scott.jewell@vai.org and}

Aditi Bagchi, St. Jude Children's Research Hospital, 262 Danny Thomas
Place MS260, Memphis, TN 38105, Tel: 901-595-7118; FAX: 901-595-8037
email: aditi.bagchi@Stjude.org

\textbf{Word Count:} a) Abstract- 98

b) Main Text -- 1235

1 Table

1 Figure

1 Supporting Figure

1 Supporting W document (Detail methods)

\textbf{Running Title:} Implications of tumor mutational burden in
medulloblastoma

\textbf{Key Words:} exome, genome, hypermutation, immune checkpoint
therapy, medulloblastoma, total mutational burden, whole genome
sequencing

\textbf{Abbreviations Key}\selectlanguage{english}
\begin{longtable}[]{@{}ll@{}}
\toprule
GATK & Genome Analysis Tool Kit\tabularnewline
\midrule
\endhead
EGA & European Genome Archive\tabularnewline
HR & Homologous recombination\tabularnewline
HRD & Homologous recombination defect\tabularnewline
Mut/Mb & Mutations per megabase\tabularnewline
MB & Medulloblastoma\tabularnewline
SMI & Small molecule inhibitor\tabularnewline
TMB & Tumor mutational burden\tabularnewline
WGS & Whole genome sequencing\tabularnewline
\bottomrule
\end{longtable}

Presented as a Platform presentation in ASPHO May 2018\selectlanguage{english}
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