Oncogenic structural aberration landscape in gastric cancer genomes.
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
22 06 2023
22 06 2023
Historique:
received:
09
03
2022
accepted:
05
06
2023
medline:
26
6
2023
pubmed:
23
6
2023
entrez:
22
6
2023
Statut:
epublish
Résumé
Structural variants (SVs) are responsible for driver events in gastric cancer (GC); however, their patterns and processes remain poorly understood. Here, we examine 170 GC whole genomes to unravel the oncogenic structural aberration landscape in GC genomes and identify six rearrangement signatures (RSs). Non-random combinations of RSs elucidate distinctive GC subtypes comprising one or a few dominant RS that are associated with specific driver events (BRCA1/2 defects, mismatch repair deficiency, and TP53 mutation) and epidemiological backgrounds. Twenty-seven SV hotspots are identified as GC driver candidates. SV hotspots frequently constitute complexly clustered SVs involved in driver gene amplification, such as ERBB2, CCNE1, and FGFR2. Further deconstruction of the locally clustered SVs uncovers amplicon-generating profiles characterized by super-large SVs and intensive segmental amplifications, contributing to the extensive amplification of GC oncogenes. Comprehensive analyses using adjusted SV allele frequencies indicate the significant involvement of extra-chromosomal DNA in processes linked to specific RSs.
Identifiants
pubmed: 37349325
doi: 10.1038/s41467-023-39263-1
pii: 10.1038/s41467-023-39263-1
pmc: PMC10287692
doi:
Substances chimiques
BRCA1 protein, human
0
BRCA1 Protein
0
BRCA2 protein, human
0
BRCA2 Protein
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
3688Informations de copyright
© 2023. The Author(s).
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