A practical framework and online tool for mutational signature analyses show inter-tissue variation and driver dependencies.
Nat Cancer
; 1(2): 249-263, 2020 02.
Article
em En
| MEDLINE
| ID: mdl-32118208
ABSTRACT
Mutational signatures are patterns of mutations that arise during tumorigenesis. We present an enhanced, practical framework for mutational signature analyses. Applying these methods on 3,107 whole genome sequenced (WGS) primary cancers of 21 organs reveals known signatures and nine previously undescribed rearrangement signatures. We highlight inter-organ variability of signatures and present a way of visualizing that diversity, reinforcing our findings in an independent analysis of 3,096 WGS metastatic cancers. Signatures with a high level of genomic instability are dependent on TP53 dysregulation. We illustrate how uncertainty in mutational signature identification and assignment to samples affects tumor classification, reinforcing that using multiple orthogonal mutational signature data is not only beneficial, it is essential for accurate tumor stratification. Finally, we present a reference web-based tool for cancer and experimentally-generated mutational signatures, called Signal (https//signal.mutationalsignatures.com), that also supports performing mutational signature analyses.
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Texto completo:
1
Bases de dados:
MEDLINE
Assunto principal:
Neoplasias
Tipo de estudo:
Prognostic_studies
Limite:
Humans
Idioma:
En
Revista:
Nat Cancer
Ano de publicação:
2020
Tipo de documento:
Article
País de afiliação:
Reino Unido