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@ARTICLE{Rausch:275428,
author = {T. Rausch and R. Snajder$^*$ and A. Leger and M.
Simovic$^*$ and M. Giurgiu and L. Villacorta and A. G.
Henssen$^*$ and S. Fröhling$^*$ and O. Stegle$^*$ and E.
Birney and M. J. Bonder$^*$ and A. Ernst$^*$ and J.
Korbel$^*$},
title = {{L}ong-read sequencing of diagnosis and post-therapy
medulloblastoma reveals complex rearrangement patterns and
epigenetic signatures},
journal = {Cell genomics},
volume = {3},
number = {4},
issn = {2666-979X},
address = {Amsterdam},
publisher = {Elsevier},
reportid = {DKFZ-2023-00751},
pages = {100281},
year = {2023},
note = {#EA:B260#LA:B420#LA:B480#},
abstract = {Cancer genomes harbor a broad spectrum of structural
variants (SVs) driving tumorigenesis, a relevant subset of
which escape discovery using short-read sequencing. We
employed Oxford Nanopore Technologies (ONT) long-read
sequencing in a paired diagnostic and post-therapy
medulloblastoma to unravel the haplotype-resolved somatic
genetic and epigenetic landscape. We assembled complex
rearrangements, including a 1.55-Mbp chromothripsis event,
and we uncover a complex SV pattern termed templated
insertion (TI) thread, characterized by short (mostly <1 kb)
insertions showing prevalent self-concatenation into highly
amplified structures of up to 50 kbp in size. TI threads
occur in $3\%$ of cancers, with a prevalence up to $74\%$ in
liposarcoma, and frequent colocalization with
chromothripsis. We also perform long-read-based methylome
profiling and discover allele-specific methylation (ASM)
effects, complex rearrangements exhibiting differential
methylation, and differential promoter methylation in
cancer-driver genes. Our study shows the advantage of
long-read sequencing in the discovery and characterization
of complex somatic rearrangements.},
cin = {B260 / B420 / HD01 / B340 / B480 / BE01},
ddc = {610},
cid = {I:(DE-He78)B260-20160331 / I:(DE-He78)B420-20160331 /
I:(DE-He78)HD01-20160331 / I:(DE-He78)B340-20160331 /
I:(DE-He78)B480-20160331 / I:(DE-He78)BE01-20160331},
pnm = {312 - Funktionelle und strukturelle Genomforschung
(POF4-312)},
pid = {G:(DE-HGF)POF4-312},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:37082141},
doi = {10.1016/j.xgen.2023.100281},
url = {https://inrepo02.dkfz.de/record/275428},
}