Identifying colorectal cancer caused by biallelic MUTYH pathogenic variants using tumor mutational signatures

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dc.citation.issue1
dc.citation.volume13
dc.contributor.authorGeorgeson P
dc.contributor.authorHarrison TA
dc.contributor.authorPope BJ
dc.contributor.authorZaidi SH
dc.contributor.authorQu C
dc.contributor.authorSteinfelder RS
dc.contributor.authorLin Y
dc.contributor.authorJoo JE
dc.contributor.authorMahmood K
dc.contributor.authorClendenning M
dc.contributor.authorWalker R
dc.contributor.authorAmitay EL
dc.contributor.authorBerndt SI
dc.contributor.authorBrenner H
dc.contributor.authorCampbell PT
dc.contributor.authorCao Y
dc.contributor.authorChan AT
dc.contributor.authorChang-Claude J
dc.contributor.authorDoheny KF
dc.contributor.authorDrew DA
dc.contributor.authorFigueiredo JC
dc.contributor.authorFrench AJ
dc.contributor.authorGallinger S
dc.contributor.authorGiannakis M
dc.contributor.authorGiles GG
dc.contributor.authorGsur A
dc.contributor.authorGunter MJ
dc.contributor.authorHoffmeister M
dc.contributor.authorHsu L
dc.contributor.authorHuang W-Y
dc.contributor.authorLimburg P
dc.contributor.authorManson JE
dc.contributor.authorMoreno V
dc.contributor.authorNassir R
dc.contributor.authorNowak JA
dc.contributor.authorObón-Santacana M
dc.contributor.authorOgino S
dc.contributor.authorPhipps AI
dc.contributor.authorPotter JD
dc.contributor.authorSchoen RE
dc.contributor.authorSun W
dc.contributor.authorToland AE
dc.contributor.authorTrinh QM
dc.contributor.authorUgai T
dc.contributor.authorMacrae FA
dc.contributor.authorRosty C
dc.contributor.authorHudson TJ
dc.contributor.authorJenkins MA
dc.contributor.authorThibodeau SN
dc.contributor.authorWinship IM
dc.contributor.authorPeters U
dc.contributor.authorBuchanan DD
dc.coverage.spatialEngland
dc.date.accessioned2023-07-05T22:44:12Z
dc.date.available2022-05-24
dc.date.available2023-07-05T22:44:12Z
dc.date.issued2022-06-06
dc.description(c) The Author/s
dc.description.abstractCarriers of germline biallelic pathogenic variants in the MUTYH gene have a high risk of colorectal cancer. We test 5649 colorectal cancers to evaluate the discriminatory potential of a tumor mutational signature specific to MUTYH for identifying biallelic carriers and classifying variants of uncertain clinical significance (VUS). Using a tumor and matched germline targeted multi-gene panel approach, our classifier identifies all biallelic MUTYH carriers and all known non-carriers in an independent test set of 3019 colorectal cancers (accuracy = 100% (95% confidence interval 99.87-100%)). All monoallelic MUTYH carriers are classified with the non-MUTYH carriers. The classifier provides evidence for a pathogenic classification for two VUS and a benign classification for five VUS. Somatic hotspot mutations KRAS p.G12C and PIK3CA p.Q546K are associated with colorectal cancers from biallelic MUTYH carriers compared with non-carriers (p = 2 × 10-23 and p = 6 × 10-11, respectively). Here, we demonstrate the potential application of mutational signatures to tumor sequencing workflows to improve the identification of biallelic MUTYH carriers.
dc.description.publication-statusPublished online
dc.format.extent3254 - ?
dc.identifierhttps://www.ncbi.nlm.nih.gov/pubmed/35668106
dc.identifier10.1038/s41467-022-30916-1
dc.identifier.citationNat Commun, 2022, 13 (1), pp. 3254 - ?
dc.identifier.doi10.1038/s41467-022-30916-1
dc.identifier.eissn2041-1723
dc.identifier.elements-id453973
dc.identifier.harvestedMassey_Dark
dc.languageeng
dc.publisherSpringer Nature Limited
dc.relation.isPartOfNat Commun
dc.rightsCC BY 4.0
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.subjectColorectal Neoplasms
dc.subjectDNA Glycosylases
dc.subjectDNA Mutational Analysis
dc.subjectGenetic Predisposition to Disease
dc.subjectGerm-Line Mutation
dc.subjectHeterozygote
dc.subjectHumans
dc.subjectMutation
dc.titleIdentifying colorectal cancer caused by biallelic MUTYH pathogenic variants using tumor mutational signatures
dc.typeJournal article
pubs.notesNot known
pubs.organisational-group/Massey University
pubs.organisational-group/Massey University/College of Health
pubs.organisational-group/Massey University/College of Health/Research Centre for Hauora and Health
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