| Literature DB >> 32118208 |
Andrea Degasperi1,2,3, Tauanne Dias Amarante1,2,3, Jan Czarnecki1,2,3, Scott Shooter1,2,3, Xueqing Zou1,2,3, Dominik Glodzik3,4,5, Sandro Morganella3,6, Arjun S Nanda2, Cherif Badja1,2,3, Gene Koh1,2,3, Sophie E Momen1,2, Ilias Georgakopoulos-Soares3, João M L Dias1, Jamie Young1,2,3, Yasin Memari1,2, Helen Davies1,2,3, Serena Nik-Zainal7,8,9.
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.Entities:
Keywords: Mutational signatures; homologous recombination deficiency; somatic variants; whole genome sequencing
Mesh：
Year: 2020 PMID： 32118208 PMCID： PMC7048622 DOI： 10.1038/s43018-020-0027-5
Source DB: PubMed Journal: Nat Cancer ISSN： 2662-1347