Näytä suppeat kuvailutiedot

dc.contributor.authorAhadova, Aysel
dc.contributor.authorPfuderer, Pauline Luise
dc.contributor.authorAhtiainen, Maarit
dc.contributor.authorBallhausen, Alexej
dc.contributor.authorBohaumilitzky, Lena
dc.contributor.authorKösegi, Svenja
dc.contributor.authorMüller, Nico
dc.contributor.authorTang, Yee Lin
dc.contributor.authorKosmalla, Kosima
dc.contributor.authorWitt, Johannes
dc.contributor.authorEndris, Volker
dc.contributor.authorStenzinger, Albrecht
dc.contributor.authorvon Knebel Doeberitz, Magnus
dc.contributor.authorBläker, Hendrik
dc.contributor.authorRenkonen-Sinisalo, Laura
dc.contributor.authorLepistö, Anna
dc.contributor.authorBöhm, Jan
dc.contributor.authorMecklin, Jukka-Pekka
dc.contributor.authorSeppälä, Toni T.
dc.contributor.authorKloor, Matthias
dc.date.accessioned2021-06-15T08:19:27Z
dc.date.available2021-06-15T08:19:27Z
dc.date.issued2021
dc.identifier.citationAhadova, A., Pfuderer, P. L., Ahtiainen, M., Ballhausen, A., Bohaumilitzky, L., Kösegi, S., Müller, N., Tang, Y. L., Kosmalla, K., Witt, J., Endris, V., Stenzinger, A., von Knebel Doeberitz, M., Bläker, H., Renkonen-Sinisalo, L., Lepistö, A., Böhm, J., Mecklin, J.-P., Seppälä, T. T., & Kloor, M. (2021). Distinct Mutational Profile of Lynch Syndrome Colorectal Cancers Diagnosed under Regular Colonoscopy Surveillance. <i>Journal of Clinical Medicine</i>, <i>10</i>(11), Article 2458. <a href="https://doi.org/10.3390/jcm10112458" target="_blank">https://doi.org/10.3390/jcm10112458</a>
dc.identifier.otherCONVID_97829188
dc.identifier.urihttps://jyx.jyu.fi/handle/123456789/76535
dc.description.abstractRegular colonoscopy even with short intervals does not prevent all colorectal cancers (CRC) in Lynch syndrome (LS). In the present study, we asked whether cancers detected under regular colonoscopy surveillance (incident cancers) are phenotypically different from cancers detected at first colonoscopy (prevalent cancers). We analyzed clinical, histological, immunological and mutational characteristics, including panel sequencing and high-throughput coding microsatellite (cMS) analysis, in 28 incident and 67 prevalent LS CRCs (n total = 95). Incident cancers presented with lower UICC and T stage compared to prevalent cancers (p < 0.0005). The majority of incident cancers (21/28) were detected after previous colonoscopy without any pathological findings. On the molecular level, incident cancers presented with a significantly lower KRAS codon 12/13 (1/23, 4.3% vs. 11/21, 52%; p = 0.0005) and pathogenic TP53 mutation frequency (0/17, 0% vs. 7/21, 33.3%; p = 0.0108,) compared to prevalent cancers; 10/17 (58.8%) incident cancers harbored one or more truncating APC mutations, all showing mutational signatures of mismatch repair (MMR) deficiency. The proportion of MMR deficiency-related mutational events was significantly higher in incident compared to prevalent CRC (p = 0.018). In conclusion, our study identifies a set of features indicative of biological differences between incident and prevalent cancers in LS, which should further be monitored in prospective LS screening studies to guide towards optimized prevention protocols.en
dc.format.mimetypeapplication/pdf
dc.language.isoeng
dc.publisherMDPI AG
dc.relation.ispartofseriesJournal of Clinical Medicine
dc.rightsCC BY 4.0
dc.subject.otherLynch syndrome
dc.subject.othercolorectal cancer
dc.subject.othercarcinogenesis
dc.subject.othercancer prevention
dc.subject.othercolonoscopy screening
dc.subject.otherincident cancer
dc.subject.othermicrosatellite instability
dc.subject.othermismatch repair deficiency
dc.subject.othermutational profiling
dc.titleDistinct Mutational Profile of Lynch Syndrome Colorectal Cancers Diagnosed under Regular Colonoscopy Surveillance
dc.typearticle
dc.identifier.urnURN:NBN:fi:jyu-202106153736
dc.contributor.laitosLiikuntatieteellinen tiedekuntafi
dc.contributor.laitosFaculty of Sport and Health Sciencesen
dc.type.urihttp://purl.org/eprint/type/JournalArticle
dc.type.coarhttp://purl.org/coar/resource_type/c_2df8fbb1
dc.description.reviewstatuspeerReviewed
dc.relation.issn2077-0383
dc.relation.numberinseries11
dc.relation.volume10
dc.type.versionpublishedVersion
dc.rights.copyright© 2021 the Authors
dc.rights.accesslevelopenAccessfi
dc.subject.ysoLynchin oireyhtymä
dc.subject.ysokoloskopia
dc.subject.ysosuolistosyövät
dc.subject.ysomikrosatelliitit
dc.subject.ysobiomarkkerit
dc.subject.ysomutaatiot
dc.subject.ysosyöpäsolut
dc.subject.ysopaksusuolisyöpä
dc.format.contentfulltext
jyx.subject.urihttp://www.yso.fi/onto/yso/p23697
jyx.subject.urihttp://www.yso.fi/onto/yso/p1078
jyx.subject.urihttp://www.yso.fi/onto/yso/p25845
jyx.subject.urihttp://www.yso.fi/onto/yso/p12287
jyx.subject.urihttp://www.yso.fi/onto/yso/p12288
jyx.subject.urihttp://www.yso.fi/onto/yso/p15346
jyx.subject.urihttp://www.yso.fi/onto/yso/p23898
jyx.subject.urihttp://www.yso.fi/onto/yso/p5937
dc.rights.urlhttps://creativecommons.org/licenses/by/4.0/
dc.relation.doi10.3390/jcm10112458
jyx.fundinginformationThis research was funded by the Wilhelm Sander Foundation (grant number 2016.056.1), Emil Aaltonen Foundation, Finnish Medical Foundation, Sigrid Juselius Foundation, Finnish State Research Funds (VTR), the Finnish Cancer Foundation and Jane and Aatos Erkko Foundation. The funders had no role in study design, data collection and analysis, decision to publish or preparation of the manuscript.
dc.type.okmA1


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