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dc.contributor.authorMäki‐Nevala, Satu
dc.contributor.authorUkwattage, Sanjeevi
dc.contributor.authorOlkinuora, Alisa
dc.contributor.authorAlmusa, Henrikki
dc.contributor.authorAhtiainen, Maarit
dc.contributor.authorRistimäki, Ari
dc.contributor.authorSeppälä, Toni
dc.contributor.authorLepistö, Anna
dc.contributor.authorMecklin, Jukka‐Pekka
dc.contributor.authorPeltomäki, Päivi
dc.date.accessioned2021-04-23T09:51:41Z
dc.date.available2021-04-23T09:51:41Z
dc.date.issued2021
dc.identifier.citationMäki‐Nevala, S., Ukwattage, S., Olkinuora, A., Almusa, H., Ahtiainen, M., Ristimäki, A., Seppälä, T., Lepistö, A., Mecklin, J., & Peltomäki, P. (2021). Somatic mutation profiles as molecular classifiers of ulcerative colitis‐associated colorectal cancer. <i>International Journal of Cancer</i>, <i>148</i>(12), 2997-3007. <a href="https://doi.org/10.1002/ijc.33492" target="_blank">https://doi.org/10.1002/ijc.33492</a>
dc.identifier.otherCONVID_51355012
dc.identifier.urihttps://jyx.jyu.fi/handle/123456789/75179
dc.description.abstractUlcerative colitis increases colorectal cancer risk by mechanisms that remain incompletely understood. We approached this question by determining the genetic and epigenetic profiles of colitis‐associated colorectal carcinomas (CA‐CRC). The findings were compared to Lynch syndrome (LS), a different form of cancer predisposition that shares the importance of immunological factors in tumorigenesis. CA‐CRCs (n=27) were investigated for microsatellite instability, CpG island methylator phenotype, and somatic mutations of 999 cancer‐relevant genes (“Pan‐cancer” panel). A subpanel of “Pan‐cancer” design (578 genes) was used for LS colorectal tumors (n=28). Mutational loads and signatures stratified CA‐CRCs into three subgroups: hypermutated microsatellite‐unstable (group 1, n=1), hypermutated microsatellite‐stable (group 2, n=9), and non‐hypermutated microsatellite‐stable (group 3, n=17). The group 1 tumor was the only one with MLH1 promoter hypermethylation and exhibited the mismatch repair deficiency‐associated signatures 21 and 15. Signatures 30 and 32 characterized group 2, whereas no prominent single signature existed in group 3. TP53, the most common mutational target in CA‐CRC (16/27, 59%), was similarly affected in groups 2 and 3, but DNA repair genes and Wnt signaling genes were mutated significantly more often in group 2. In LS tumors, the degree of hypermutability exceeded that of the hypermutated CA‐CRC groups 1 and 2, and somatic mutational profiles and signatures were different. In conclusion, groups 1 (4%) and 3 (63%) comply with published studies, whereas group 2 (33%) is novel. The existence of molecularly distinct subgroups within CA‐CRC may guide clinical management, such as therapy options.en
dc.format.mimetypeapplication/pdf
dc.languageeng
dc.language.isoeng
dc.publisherJohn Wiley & Sons
dc.relation.ispartofseriesInternational Journal of Cancer
dc.rightsCC BY 4.0
dc.subject.otherulcerative colitis
dc.subject.otherLynch syndrome
dc.subject.othercolorectal cancer
dc.subject.othermicrosatellite instability
dc.subject.othersomatic mutation
dc.titleSomatic mutation profiles as molecular classifiers of ulcerative colitis‐associated colorectal cancer
dc.typearticle
dc.identifier.urnURN:NBN:fi:jyu-202104232473
dc.contributor.laitosLiikuntatieteellinen tiedekuntafi
dc.contributor.laitosFaculty of Sport and Health Sciencesen
dc.type.urihttp://purl.org/eprint/type/JournalArticle
dc.description.reviewstatuspeerReviewed
dc.format.pagerange2997-3007
dc.relation.issn0020-7136
dc.relation.numberinseries12
dc.relation.volume148
dc.type.versionpublishedVersion
dc.rights.copyright© 2021 The Authors. International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC.
dc.rights.accesslevelopenAccessfi
dc.subject.ysoLynchin oireyhtymä
dc.subject.ysomutaatiot
dc.subject.ysoDNA-analyysi
dc.subject.ysosyöpätaudit
dc.subject.ysotulehdukselliset suolistosairaudet
dc.subject.ysomikrosatelliitit
dc.subject.ysosuolistosyövät
dc.format.contentfulltext
jyx.subject.urihttp://www.yso.fi/onto/yso/p23697
jyx.subject.urihttp://www.yso.fi/onto/yso/p15346
jyx.subject.urihttp://www.yso.fi/onto/yso/p25695
jyx.subject.urihttp://www.yso.fi/onto/yso/p678
jyx.subject.urihttp://www.yso.fi/onto/yso/p38636
jyx.subject.urihttp://www.yso.fi/onto/yso/p12287
jyx.subject.urihttp://www.yso.fi/onto/yso/p25845
dc.rights.urlhttps://creativecommons.org/licenses/by/4.0/
dc.relation.doi10.1002/ijc.33492
jyx.fundinginformationThis study was supported by Jane and Aatos Erkko Foundation (to PP and J-PM); the Academy of Finland (grant numbers 294643 and 330606 to PP and 331284 to SM-N); the Finnish Cancer Foundation (to PP, J-PM and AR); the Sigrid Juselius Foundation (to PP and AR) and the HiLIFE Fellows 2017 – 2020 (to PP).


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