Clinical and Experimental Medicine

, Volume 19, Issue 3, pp 393–400 | Cite as

Mutation analysis of POLE gene in patients with early-onset colorectal cancer revealed a rare silent variant within the endonuclease domain with potential effect on splicing

  • Zora LasabováEmail author
  • Michal Kalman
  • Veronika Holubeková
  • Marián Grendár
  • Ivana Kašubová
  • Karin Jašek
  • Sandra Meršaková
  • Bibiana Malicherová
  • Denis Baranenko
  • Mariusz Adamek
  • Peter KruzliakEmail author
  • Lukáš Plank
Original Article


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.


Early-onset colorectal cancer POLE mutations Microsatellite instability Tumor-infiltrating lymphocytes 



This study was supported by the Biomedical center Martin (ITMS 26220220187), which is co-financed from EU sources, by Government of Russian Federation, Grant 08-08, and by the projects of the Slovak Research and development Agency APVV Grant APVV-16-0066, and VEGA Grants 1/0199/17 and 1/0380/18.

Compliance with ethical standards

Conflict of interest

All authors declare no conflict of interest.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed consent

Informed consent was obtained from all individual participants included in the study.


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Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  • Zora Lasabová
    • 1
    • 2
    Email author
  • Michal Kalman
    • 3
  • Veronika Holubeková
    • 1
  • Marián Grendár
    • 4
  • Ivana Kašubová
    • 1
  • Karin Jašek
    • 1
  • Sandra Meršaková
    • 1
  • Bibiana Malicherová
    • 1
  • Denis Baranenko
    • 5
  • Mariusz Adamek
    • 6
  • Peter Kruzliak
    • 7
    Email author
  • Lukáš Plank
    • 3
  1. 1.Division of Oncology, Biomedical Center Martin, Jessenius Faculty of Medicine in MartinComenius University in BratislavaMartinSlovakia
  2. 2.Department of Molecular Biology and Genomics, Jessenius Faculty of Medicine in MartinComenius University in BratislavaMartinSlovakia
  3. 3.Department of Pathological Anatomy, Jessenius Faculty of Medicine University Hospital in MartinComenius University in BratislavaMartinSlovakia
  4. 4.Department of Bioinformatics, Biomedical Center Martin, Jessenius Faculty of Medicine in MartinComenius University in BratislavaMartinSlovakia
  5. 5.International Research Centre “Biotechnologies of the Third Millennium”ITMO UniversitySaint-PetersburgRussian Federation
  6. 6.Department of Thoracic Surgery, Faculty of Medicine and DentistryMedical University of SilesiaKatowicePoland
  7. 7.Department of Internal MedicineBrothers of Mercy HospitalBrnoCzech Republic

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