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

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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

Title: Distinct Mutational Profile of Lynch Syndrome Colorectal Cancers Diagnosed under Regular Colonoscopy Surveillance
Author: Ahadova, Aysel; Pfuderer, Pauline Luise; Ahtiainen, Maarit; Ballhausen, Alexej; Bohaumilitzky, Lena; Kösegi, Svenja; Müller, Nico; Tang, Yee Lin; Kosmalla, Kosima; Witt, Johannes; Endris, Volker; Stenzinger, Albrecht; von Knebel Doeberitz, Magnus; Bläker, Hendrik; Renkonen-Sinisalo, Laura; Lepistö, Anna; Böhm, Jan; Mecklin, Jukka-Pekka; Seppälä, Toni T.; Kloor, Matthias
Contributor organization: Staff Services
HUS Abdominal Center
Department of Surgery
Genome-Scale Biology (GSB) Research Program
II kirurgian klinikka
Digital Precision Cancer Medicine (iCAN)
ATG - Applied Tumor Genomics
Date: 2021-06
Language: eng
Number of pages: 17
Belongs to series: Journal of clinical medicine
ISSN: 2077-0383
DOI: https://doi.org/10.3390/jcm10112458
URI: http://hdl.handle.net/10138/333561
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.
Lynch syndrome
cancer prevention
colonoscopy screening
colorectal cancer
incident cancer
microsatellite instability
mismatch repair deficiency
mutational profiling
3126 Surgery, anesthesiology, intensive care, radiology
3121 General medicine, internal medicine and other clinical medicine
Peer reviewed: Yes
Rights: cc_by
Usage restriction: openAccess
Self-archived version: publishedVersion

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