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dc.contributor.authorCucco, Francescoen
dc.contributor.authorBarrans, Sharonen
dc.contributor.authorSha, Chulinen
dc.contributor.authorClipson, Alexandraen
dc.contributor.authorCrouch, Simonen
dc.contributor.authorDobson, Rachelen
dc.contributor.authorChen, Zien
dc.contributor.authorThompson, Joe Sneathen
dc.contributor.authorCare, Matthew Aen
dc.contributor.authorCummin, Thomasen
dc.contributor.authorCaddy, Joshen
dc.contributor.authorLiu, Hongxiangen
dc.contributor.authorRobinson, Anneen
dc.contributor.authorSchuh, Annaen
dc.contributor.authorFitzgibbon, Judeen
dc.contributor.authorPainter, Danielen
dc.contributor.authorSmith, Alexandraen
dc.contributor.authorRoman, Eveen
dc.contributor.authorTooze, Reubenen
dc.contributor.authorBurton, Catherineen
dc.contributor.authorDavies, Andrew Jen
dc.contributor.authorWesthead, David Ren
dc.contributor.authorJohnson, Peter WMen
dc.contributor.authorDu, Ming-Qingen
dc.date.accessioned2019-11-23T00:31:42Z
dc.date.available2019-11-23T00:31:42Z
dc.date.issued2020-05en
dc.identifier.issn0887-6924
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/299198
dc.description.abstractUsing a Burkitt lymphoma-like gene expression signature, we recently defined a high-risk molecular high-grade (MHG) group mainly within germinal centre B-cell like diffuse large B-cell lymphomas (GCB-DLBCL), which was enriched for MYC/BCL2 double-hit (MYC/BCL2-DH). The genetic basis underlying MHG-DLBCL and their aggressive clinical behaviour remain unknown. We investigated 697 cases of DLBCL, particularly those with MYC/BCL2-DH (n=62) by targeted sequencing and gene expression profiling. We showed that DLBCL with MYC/BCL2-DH, and those with BCL2 translocation, harbour the characteristic mutation signatures that are associated with follicular lymphoma and its high-grade transformation. We identified frequent MYC hotspot mutations that affect the phosphorylation site (T58) and its adjacent amino acids, which are important for MYC protein degradation. These MYC mutations were seen in a subset of cases with MYC translocation, but predominantly in those of MHG. The mutations were more frequent in double-hit lymphomas with IG as the MYC translocation partner, and were associated with higher MYC protein expression and poor patient survival. DLBCL with MYC/BCL2-DH and those with BCL2 translocation alone are most likely derived from follicular lymphoma or its precursor lesion, and acquisition of MYC pathogenic mutations may augment MYC function, resulting in aggressive clinical behaviour.
dc.format.mediumPrint-Electronicen
dc.languageengen
dc.publisherSpringer Nature
dc.rightsAttribution 4.0 International
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.subjectHumansen
dc.subjectTranslocation, Geneticen
dc.subjectProto-Oncogene Proteins c-mycen
dc.subjectProto-Oncogene Proteins c-bcl-2en
dc.subjectPrognosisen
dc.subjectSurvival Rateen
dc.subjectGene Expression Profilingen
dc.subjectGene Expression Regulation, Leukemicen
dc.subjectGene Rearrangementen
dc.subjectPhenotypeen
dc.subjectMutationen
dc.subjectMiddle Ageden
dc.subjectFemaleen
dc.subjectMaleen
dc.subjectLymphoma, Large B-Cell, Diffuseen
dc.subjectClonal Evolutionen
dc.subjectBiomarkers, Tumoren
dc.titleDistinct genetic changes reveal evolutionary history and heterogeneous molecular grade of DLBCL with MYC/BCL2 double-hit.en
dc.typeArticle
prism.endingPage1341
prism.issueIdentifier5en
prism.publicationDate2020en
prism.publicationNameLeukemiaen
prism.startingPage1329
prism.volume34en
dc.identifier.doi10.17863/CAM.46263
dcterms.dateAccepted2019-12-06en
rioxxterms.versionofrecord10.1038/s41375-019-0691-6en
rioxxterms.versionVoR
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/all-rights-reserveden
rioxxterms.licenseref.startdate2020-05en
dc.contributor.orcidCare, Matthew A [0000-0001-6584-5889]
dc.contributor.orcidFitzgibbon, Jude [0000-0002-9069-1866]
dc.contributor.orcidRoman, Eve [0000-0001-7603-3704]
dc.contributor.orcidTooze, Reuben [0000-0003-2915-7119]
dc.contributor.orcidDavies, Andrew J [0000-0002-7517-6938]
dc.contributor.orcidWesthead, David R [0000-0002-0519-3820]
dc.contributor.orcidJohnson, Peter WM [0000-0003-2306-4974]
dc.identifier.eissn1476-5551
rioxxterms.typeJournal Article/Reviewen
pubs.funder-project-idBloodwise (via University of Southampton) (515010)
pubs.funder-project-idBloodwise (15019)
cam.orpheus.successThu Jan 30 10:35:23 GMT 2020 - Embargo updated*
rioxxterms.freetoread.startdate2100-01-01


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Attribution 4.0 International
Except where otherwise noted, this item's licence is described as Attribution 4.0 International