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A practical framework and online tool for mutational signature analyses show intertissue variation and driver dependencies

Degasperi, Andrea (author)
Wellcome Trust Sanger Institute,Addenbrooke's Hospital
Amarante, Tauanne Dias (author)
Addenbrooke's Hospital,Wellcome Trust Sanger Institute
Czarnecki, Jan (author)
Wellcome Trust Sanger Institute,Addenbrooke's Hospital
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Shooter, Scott (author)
Wellcome Trust Sanger Institute,Addenbrooke's Hospital
Zou, Xueqing (author)
Wellcome Trust Sanger Institute,Addenbrooke's Hospital
Glodzik, Dominik (author)
Lund University,Lunds universitet,Bröstcancer-genetik,Sektion I,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Forskningsgrupp Lungcancer,Forskargrupper vid Lunds universitet,Breastcancer-genetics,Section I,Department of Clinical Sciences, Lund,Faculty of Medicine,Research Group Lung Cancer,Lund University Research Groups,Memorial Sloan-Kettering Cancer Center,Wellcome Trust Sanger Institute
Morganella, Sandro (author)
Wellcome Trust Sanger Institute
Nanda, Arjun S. (author)
Addenbrooke's Hospital
Badja, Cherif (author)
Wellcome Trust Sanger Institute,Addenbrooke's Hospital
Koh, Gene (author)
Addenbrooke's Hospital,Wellcome Trust Sanger Institute
Momen, Sophie E. (author)
Addenbrooke's Hospital
Georgakopoulos-Soares, Ilias (author)
Wellcome Trust Sanger Institute
Dias, João M.L. (author)
Young, Jamie (author)
Addenbrooke's Hospital,Wellcome Trust Sanger Institute
Memari, Yasin (author)
Addenbrooke's Hospital
Davies, Helen (author)
Addenbrooke's Hospital,Wellcome Trust Sanger Institute
Nik-Zainal, Serena (author)
Addenbrooke's Hospital,Wellcome Trust Sanger Institute
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 (creator_code:org_t)
2020-02-17
2020
English 15 s.
In: Nature Cancer. - : Springer Science and Business Media LLC. - 2662-1347. ; 1:2, s. 249-263
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  • Journal article (peer-reviewed)
Abstract Subject headings
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  • Mutational signatures are patterns of mutations that arise during tumorigenesis. We present an enhanced, practical framework for mutational signature analyses. Applying these methods to 3,107 whole-genome-sequenced (WGS) primary cancers of 21 organs reveals known signatures and nine previously undescribed rearrangement signatures. We highlight interorgan 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, but is also 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.

Subject headings

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Cancer and Oncology (hsv//eng)

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