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 Molecular Biology and Genomics Jessenius Faculty of Medicine in Martin Comenius University in Bratislava Martin Slovakia

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

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

Zobrazit více v PubMed

Gastroenterology. 2007 Jul;133(1):48-56 PubMed

Am J Surg Pathol. 2010 Dec;34(12):1820-9 PubMed

Int J Colorectal Dis. 2012 Jan;27(1):71-9 PubMed

Nature. 2012 Jul 18;487(7407):330-7 PubMed

Nat Genet. 2013 Feb;45(2):136-44 PubMed

Hum Mol Genet. 2013 Jul 15;22(14):2820-8 PubMed

Nature. 2013 May 2;497(7447):67-73 PubMed

N Engl J Med. 2015 Jun 25;372(26):2509-20 PubMed

Genet Med. 2016 Apr;18(4):325-32 PubMed

JAMA Oncol. 2015 Dec;1(9):1319-23 PubMed

Nat Rev Cancer. 2016 Feb;16(2):71-81 PubMed

Oncotarget. 2016 Oct 18;7(42):68638-68649 PubMed

Virchows Arch. 2017 Jan;470(1):29-36 PubMed

J Pathol. 2017 May;242(1):10-15 PubMed

J Natl Compr Canc Netw. 2017 Feb;15(2):142-147 PubMed

Curr Treat Options Oncol. 2017 Apr;18(4):23 PubMed

Lancet Gastroenterol Hepatol. 2016 Nov;1(3):207-216 PubMed

Oncotarget. 2017 Apr 18;8(16):26732-26743 PubMed

Exp Mol Pathol. 2017 Jun;102(3):475-483 PubMed

Cancer Med. 2017 Dec;6(12):2966-2971 PubMed

Cancer Discov. 2018 Jun;8(6):730-749 PubMed

Lung Cancer. 2018 Apr;118:57-61 PubMed

J Pathol. 2018 Jul;245(3):283-296 PubMed

PLoS Med. 2018 Jun 1;15(6):e1002577 PubMed

J Gastrointest Oncol. 2018 Jun;9(3):404-415 PubMed

J Gastrointest Oncol. 2018 Aug;9(4):E23-E27 PubMed

CA Cancer J Clin. 2018 Nov;68(6):394-424 PubMed

Am J Transl Res. 2018 Nov 15;10(11):3773-3781 PubMed

Oncol Lett. 2019 Apr;17(4):3649-3656 PubMed

Genomic profile and immune contexture in colorectal cancer-relevance for prognosis and immunotherapy

Genetic and epigenetic analysis of the beta-2-microglobulin gene in microsatellite instable colorectal cancer