Unravelling mutational signatures with plasma circulating tumour DNA

Abstract The use of circulating tumour DNA (ctDNA) to profile mutational signatures represents a non-invasive opportunity for understanding cancer mutational processes. Here we present MisMatchFinder, a liquid biopsy approach for mutational signature detection using low-coverage whole-genome sequenc...

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Main Authors: Sebastian Hollizeck, Ning Wang, Stephen Q. Wong, Cassandra Litchfield, Jerick Guinto, Sarah Ftouni, Richard Rebello, Sehrish Kanwal, Ruining Dong, Sean Grimmond, Shahneen Sandhu, Linda Mileshkin, Richard W. Tothill, Dineika Chandrananda, Sarah-Jane Dawson
Format: Article
Language:English
Published: Nature Portfolio 2024-11-01
Series:Nature Communications
Online Access:https://doi.org/10.1038/s41467-024-54193-2
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author Sebastian Hollizeck
Ning Wang
Stephen Q. Wong
Cassandra Litchfield
Jerick Guinto
Sarah Ftouni
Richard Rebello
Sehrish Kanwal
Ruining Dong
Sean Grimmond
Shahneen Sandhu
Linda Mileshkin
Richard W. Tothill
Dineika Chandrananda
Sarah-Jane Dawson
author_facet Sebastian Hollizeck
Ning Wang
Stephen Q. Wong
Cassandra Litchfield
Jerick Guinto
Sarah Ftouni
Richard Rebello
Sehrish Kanwal
Ruining Dong
Sean Grimmond
Shahneen Sandhu
Linda Mileshkin
Richard W. Tothill
Dineika Chandrananda
Sarah-Jane Dawson
author_sort Sebastian Hollizeck
collection DOAJ
description Abstract The use of circulating tumour DNA (ctDNA) to profile mutational signatures represents a non-invasive opportunity for understanding cancer mutational processes. Here we present MisMatchFinder, a liquid biopsy approach for mutational signature detection using low-coverage whole-genome sequencing of ctDNA. Through analysis of 375 plasma samples across 9 cancers, we demonstrate that MisMatchFinder accurately infers single-base and doublet-base substitutions, as well as insertions and deletions to enhance the detection of ctDNA and clinically relevant mutational signatures.
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spelling doaj-art-db7a898b61ab4233a1819ffabcbe623b2024-11-17T12:35:58ZengNature PortfolioNature Communications2041-17232024-11-011511910.1038/s41467-024-54193-2Unravelling mutational signatures with plasma circulating tumour DNASebastian Hollizeck0Ning Wang1Stephen Q. Wong2Cassandra Litchfield3Jerick Guinto4Sarah Ftouni5Richard Rebello6Sehrish Kanwal7Ruining Dong8Sean Grimmond9Shahneen Sandhu10Linda Mileshkin11Richard W. Tothill12Dineika Chandrananda13Sarah-Jane Dawson14Peter MacCallum Cancer CentrePeter MacCallum Cancer CentrePeter MacCallum Cancer CentrePeter MacCallum Cancer CentrePeter MacCallum Cancer CentrePeter MacCallum Cancer CentreCentre for Cancer Research, The University of MelbourneCentre for Cancer Research, The University of MelbourneCentre for Cancer Research, The University of MelbourneCentre for Cancer Research, The University of MelbournePeter MacCallum Cancer CentrePeter MacCallum Cancer CentreSir Peter MacCallum Department of Oncology, The University of MelbournePeter MacCallum Cancer CentrePeter MacCallum Cancer CentreAbstract The use of circulating tumour DNA (ctDNA) to profile mutational signatures represents a non-invasive opportunity for understanding cancer mutational processes. Here we present MisMatchFinder, a liquid biopsy approach for mutational signature detection using low-coverage whole-genome sequencing of ctDNA. Through analysis of 375 plasma samples across 9 cancers, we demonstrate that MisMatchFinder accurately infers single-base and doublet-base substitutions, as well as insertions and deletions to enhance the detection of ctDNA and clinically relevant mutational signatures.https://doi.org/10.1038/s41467-024-54193-2
spellingShingle Sebastian Hollizeck
Ning Wang
Stephen Q. Wong
Cassandra Litchfield
Jerick Guinto
Sarah Ftouni
Richard Rebello
Sehrish Kanwal
Ruining Dong
Sean Grimmond
Shahneen Sandhu
Linda Mileshkin
Richard W. Tothill
Dineika Chandrananda
Sarah-Jane Dawson
Unravelling mutational signatures with plasma circulating tumour DNA
Nature Communications
title Unravelling mutational signatures with plasma circulating tumour DNA
title_full Unravelling mutational signatures with plasma circulating tumour DNA
title_fullStr Unravelling mutational signatures with plasma circulating tumour DNA
title_full_unstemmed Unravelling mutational signatures with plasma circulating tumour DNA
title_short Unravelling mutational signatures with plasma circulating tumour DNA
title_sort unravelling mutational signatures with plasma circulating tumour dna
url https://doi.org/10.1038/s41467-024-54193-2
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