The colorectal cancer harbor germline, somatic or epimutations in mismatch repair genes, MUTYH or POLE gene, which lead to the hypermutated and ultramutator phenotypes with increased immune response. The mutations in POLE gene were reported to occur more frequently in early-onset colorectal cancer (EOCRC), and the patients are strong candidates for checkpoint inhibitor therapy. Here, we report mutation analysis within the endonuclease domain of the POLE gene in the cohort of patients with EOCRC in order to identify recurrent or new mutations and evaluate their association with the presence of tumor-infiltrating lymphocytes (TILs) and peritumoral lymphoid reaction. We have shown a significant association between MSI tumors and TILs (p = 0.004). Using sensitive single-tube nested PCR with subsequent Sanger sequencing, we have found in one female patient diagnosed at age 48 with rectal adenocarcinoma with mucinous elements staged pT3pN2pM1 a silent variant within the exon 9 NM_006231.3 c.849 C > T, NP_00622.2 p.Leu283 = recorded in dSNP as rs1232888774 with MAF = 0.00002. In silico prediction, result showed possible involvement into splicing; therefore, this rare variant can be involved into EOCRC pathogenesis. In the time of precise medicine, it is important to develop screening strategies also for less common conditions such as EOCRC allowing to predict tailored therapy for younger patients suffering from CRC that harbor mutations in the POLE gene.

Department of Bioinformatics Biomedical Center Martin Jessenius Faculty of Medicine in Martin Comenius University in Bratislava Martin Slovakia

Department of Internal Medicine Brothers of Mercy Hospital Brno Czech Republic

Department of Pathological Anatomy Jessenius Faculty of Medicine University Hospital in Martin Comenius University in Bratislava Martin Slovakia

Department of Thoracic Surgery Faculty of Medicine and Dentistry Medical University of Silesia Katowice Poland

Division of Oncology Biomedical Center Martin Jessenius Faculty of Medicine in Martin Comenius University in Bratislava Maláhora 4C 03601 Martin Slovakia

Division of Oncology Biomedical Center Martin Jessenius Faculty of Medicine in Martin Comenius University in Bratislava Maláhora 4C 03601 Martin Slovakia Department of Molecular Biology and Genomics Jessenius Faculty of Medicine in Martin Comenius University in Bratislava Martin Slovakia

International Research Centre Biotechnologies of the 3rd Millennium ITMO University Saint Petersburg Russian Federation

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