Genes & Genomics

, Volume 41, Issue 12, pp 1517–1525 | Cite as

The hTERT-VNTR2-2nd alleles are involved in genomic stability in gastrointestinal cancer

  • Jeong-Ah Kwon
  • Mi-So Jeong
  • Se-Lyun Yoon
  • Jeong-Yeon Mun
  • Min-Hye Kim
  • Gi-Eun Yang
  • Seong-Hwan Park
  • Jin-Woong Chung
  • Yung Hyun Choi
  • Hee-Jae Cha
  • Sun-Hee LeemEmail author
Research Article



hTERT contains a high density of minisatellites, of which rare alleles of hTERT-VNTR2-2nd have been reported to be associated with prostate cancer. This shows an association between VNTR and cancer, but this repeat sequence is likely to be associated with genomic instability. Therefore, we investigated the effects of hTERT-VNTR2-2nd on gastrointestinal cancer and the relationship between repeated sequence and chromosome instability.


A case–control study was performed using DNA from 818 cancer-free controls, 539 cases with gastric cancer, 275 cases with colon cancer and 274 cases with rectal cancer. To determine whether minisatellites affect gene expression, expression levels were examined using TERT-reporter vectors in cell lines. In addition, the length of the hTERT-VNTR2-2nd alleles were determined in blood and cancer tissues from 107 gastric cancers, 112 colon cancers and 76 rectal cancers patients to determine whether the repeat sequence was associated with genomic instability during cancer development.


No statistically significant association between hTERT-VNTR2-2nd and risk of gastrointestinal cancer was detected. However, it has been shown that VNTRs inserted into the enhancer region can regulate the expression of TERT in gastrointestinal cancer cells. Moreover, hTERT-VNTR2-2nd was analyzed in matched blood and cancer tissue from patients with gastrointestinal cancer and in seven among 294 subjects, and hTERT-VNTR2-2nd was found to be rearranged.


We suggest that minisatellites are associated with genomic instability in cancer and that the hTERT-VNTRs region may increase hTERT expression in gastrointestinal cancer cells.


TERT Gastrointestinal cancer Minisatellite polymorphism Genome instability 



We gratefully acknowledge patients and their caregivers for their willing participation in this project and for consenting to the use of information obtained from the study.


This work was supported by the Dong-A University research fund.

Compliance with ethical standards

Conflict of interest

Jeong-Ah Kwon, Mi-So Jeong, Se-Lyun Yoon, Jeong-Yeon Mun, Min-Hye Kim, Gi-Eun Yang, Seong-Hwan Park, Jin-Woong Chung, Yung Hyun Choi, Hee-Jae Cha and Sun-Hee Leem declare that they have no competing interests.

Ethical approval

This study was conducted with informed written consent from participants and after approval by the bioethics committees of Dong-A University Hospital (#IRB-07-10-7; Busan, Korea), Inje University Paik Hospital (#IRB11-011) and the Chungbuk National University Hospital (#IRB-2006-1; Cheongju, Korea).


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Copyright information

© The Genetics Society of Korea 2019

Authors and Affiliations

  • Jeong-Ah Kwon
    • 1
    • 2
  • Mi-So Jeong
    • 1
  • Se-Lyun Yoon
    • 1
  • Jeong-Yeon Mun
    • 1
  • Min-Hye Kim
    • 1
  • Gi-Eun Yang
    • 1
  • Seong-Hwan Park
    • 1
  • Jin-Woong Chung
    • 1
  • Yung Hyun Choi
    • 3
  • Hee-Jae Cha
    • 4
  • Sun-Hee Leem
    • 1
    Email author
  1. 1.Department of Biology and Biomedical ScienceDong-A UniversityBusanKorea
  2. 2.DNA Analysis Section, Forensic Medicine DivisionBusan Institute, National Forensic ServiceYangsanKorea
  3. 3.Department of BiochemistryDong-eui University College of Korean MedicineBusanKorea
  4. 4.Department of Parasitology and GeneticsKosin University College of MedicineBusanKorea

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