Distinct Mutational Profile of Lynch Syndrome Colorectal Cancers Diagnosed under Regular Colonoscopy Surveillance

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dc.contributor.author Ahadova, Aysel
dc.contributor.author Pfuderer, Pauline Luise
dc.contributor.author Ahtiainen, Maarit
dc.contributor.author Ballhausen, Alexej
dc.contributor.author Bohaumilitzky, Lena
dc.contributor.author Kösegi, Svenja
dc.contributor.author Müller, Nico
dc.contributor.author Tang, Yee Lin
dc.contributor.author Kosmalla, Kosima
dc.contributor.author Witt, Johannes
dc.contributor.author Endris, Volker
dc.contributor.author Stenzinger, Albrecht
dc.contributor.author von Knebel Doeberitz, Magnus
dc.contributor.author Bläker, Hendrik
dc.contributor.author Renkonen-Sinisalo, Laura
dc.contributor.author Lepistö, Anna
dc.contributor.author Böhm, Jan
dc.contributor.author Mecklin, Jukka-Pekka
dc.contributor.author Seppälä, Toni T.
dc.contributor.author Kloor, Matthias
dc.date.accessioned 2021-08-25T10:07:02Z
dc.date.available 2021-08-25T10:07:02Z
dc.date.issued 2021-06
dc.identifier.citation Ahadova , 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 ' , Journal of clinical medicine , vol. 10 , no. 11 , 2458 . https://doi.org/10.3390/jcm10112458
dc.identifier.other PURE: 165629636
dc.identifier.other PURE UUID: ad8f7ea9-118f-4df7-a54c-c1d3c3a440d3
dc.identifier.other Bibtex: jcm10112458
dc.identifier.other WOS: 000660214300001
dc.identifier.other ORCID: /0000-0002-5866-4059/work/98974649
dc.identifier.other ORCID: /0000-0002-4940-3498/work/98975042
dc.identifier.uri http://hdl.handle.net/10138/333561
dc.description.abstract Regular 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. fi
dc.format.extent 17
dc.language.iso eng
dc.relation.ispartof Journal of clinical medicine
dc.rights cc_by
dc.rights.uri info:eu-repo/semantics/openAccess
dc.subject CARCINOMAS
dc.subject DATABASE
dc.subject GUIDELINES
dc.subject HEREDITARY
dc.subject Lynch syndrome
dc.subject MSH2
dc.subject RISK
dc.subject TUMORS
dc.subject cancer prevention
dc.subject carcinogenesis
dc.subject colonoscopy screening
dc.subject colorectal cancer
dc.subject incident cancer
dc.subject microsatellite instability
dc.subject mismatch repair deficiency
dc.subject mutational profiling
dc.subject 3126 Surgery, anesthesiology, intensive care, radiology
dc.subject 3121 General medicine, internal medicine and other clinical medicine
dc.title Distinct Mutational Profile of Lynch Syndrome Colorectal Cancers Diagnosed under Regular Colonoscopy Surveillance en
dc.type Article
dc.contributor.organization Staff Services
dc.contributor.organization HUS Abdominal Center
dc.contributor.organization Department of Surgery
dc.contributor.organization Genome-Scale Biology (GSB) Research Program
dc.contributor.organization II kirurgian klinikka
dc.contributor.organization Clinicum
dc.contributor.organization Digital Precision Cancer Medicine (iCAN)
dc.contributor.organization ATG - Applied Tumor Genomics
dc.description.reviewstatus Peer reviewed
dc.relation.doi https://doi.org/10.3390/jcm10112458
dc.relation.issn 2077-0383
dc.rights.accesslevel openAccess
dc.type.version publishedVersion

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