Cancer Research and Treatment

Chang Hyeok Ahn

3 Articles

Mutational Analysis of TTK Gene in Gastric and Colorectal Cancers with Microsatellite Instability: Chang Hyeok Ahn, Yoo Ri Kim, Sung Soo Kim, Nam Jin Yoo, Sug Hyung Lee; Cancer Res Treat. 2009;41(4):224-228. Published online December 31, 2009; DOI: https://doi.org/10.4143/crt.2009.41.4.224

Purpose

The TTK gene plays a crucial role in regulation of the mitotic checkpoint. The TTK gene has an A9 mononucleotide repeat in the coding sequences, which harbors mutations in gastric (GC) and colorectal cancers (CRC) with microsatellite instability (MSI). However, there are three more repeats (the A7s) in the coding sequences that have not been analyzed. The aim of this study was to explore whether the three A7s as well as the A9 are altered in GC and CRC, and to find any association of TTK mutation with clinocopathologic characteristics of GC and CRC.

Materials and Methods

We analyzed exon 5 (A7 and A7) and exon 22 (A9 and A7) which have repeat sequences in 30 GC with high MSI (MSI-H), 15 GC with low MSI (MSI-L), 35 CRC with MSI-H, and 15 CRC with MSI-L, by single-strand conformation polymorphism (SSCP) and DNA sequencing assays.

Results

Overall, we detected 23 frameshift mutations in the repeat sequences of TTK in the GC with MSI-H (11/30; 36.7%) and the CRC with MSI-H (12/35; 34.3%), but not in the cancers with MSI-L. The mutations were observed in both A9 and A7 of exon 22, but in neither of the two A7s of exon 5. The mutations consisted of c.2560delA, c.2560dupA, c.2571delA and c.[2560delA(+)2571delA]. All of the mutations were frameshift mutations and would result in premature stops of TTK protein synthesis. There was no significant difference in clinopathologic parameters of the cancers with the mutations.

Conclusion

Our data indicate that frameshift mutations of TTK are common in both GC and CRC with MSI-H, and that the mutations occur not only in the A9 repeat but also in the A7 repeat. The data suggest that frameshift mutations of TTK might alter cell cycle control in the affected cells and contribute to pathogenesis of cancers with MSI-H.

Citations

Citations to this article as recorded by

Uncovering the underlying mechanism of yuanhuacine against colorectal cancer by transcriptomics and experimental investigations
Jingchu Li, Shanshan Liu, Jian Chen, Hanxue Wang, Xia Feng, Chenglin Jia, Jiacheng Li, Hao Yin, Jie Li, Chang Liu, Yongbing Cao, Chao Ma
Phytomedicine.2025; 140: 156570. CrossRef
Identification of Unique Long Non-Coding RNAs as Putative Biomarkers for Chromophobe Renal Cell Carcinoma
Guanlin Wu, Pengfei Xia, Shixian Yan, Dongming Chen, Lei Xie, Gang Fan
Personalized Medicine.2021; 18(1): 9. CrossRef
In-Silico Evaluation of Genetic Alterations in Ovarian Carcinoma and Therapeutic Efficacy of NSC777201, as a Novel Multi-Target Agent for TTK, NEK2, and CDK1
Harshita Nivrutti Khedkar, Yu-Chi Wang, Vijesh Kumar Yadav, Prateeti Srivastava, Bashir Lawal, Ntlotlang Mokgautsi, Maryam Rachmawati Sumitra, Alexander T. H. Wu, Hsu-Shan Huang
International Journal of Molecular Sciences.2021; 22(11): 5895. CrossRef
Reversine inhibits proliferation, invasion and migration and induces cell apoptosis in gastric cancer cells by downregulating TTK
Pengfei Xia, Jin Liang, Di Jin, Zhanyong Jin
Experimental and Therapeutic Medicine.2021;[Epub] CrossRef
Characteristic Analysis of Featured Genes Associated With Stemness Indices in Colorectal Cancer
Yongqu Lu, Xin Zhou, Zhenzhen Liu, Wendong Wang, Fei Li, Wei Fu
Frontiers in Molecular Biosciences.2020;[Epub] CrossRef
Mutations Defining Patient Cohorts With Elevated PD-L1 Expression in Gastric Cancer
Otília Menyhárt, Lőrinc Sándor Pongor, Balázs Győrffy
Frontiers in Pharmacology.2019;[Epub] CrossRef
Comprehensive Analysis of Mouse Cancer/Testis Antigen Functions in Cancer Cells and Roles of TEKT5 in Cancer Cells and Testicular Germ Cells
Nana Aoki, Yasuhisa Matsui
Molecular and Cellular Biology.2019;[Epub] CrossRef
TTK promotes mesenchymal signaling via multiple mechanisms in triple negative breast cancer
Jamie L. King, Baotong Zhang, Yixiang Li, Kathy P. Li, Jianping J. Ni, Harold I. Saavedra, Jin-Tang Dong
Oncogenesis.2018;[Epub] CrossRef
ABCB1 2677G>T/A variant enhances chemosensitivity to anti-cancer agents acting on microtubule dynamics through LAMP1 inhibition
Woo Sun Kwon, Sun Young Rha, Hei-Cheul Jeung, Joong Bae Ahn, Jae-Joon Jung, Dong Hyuk Ki, Tae Soo Kim, Hyun Cheol Chung
Biochemical Pharmacology.2017; 123: 73. CrossRef
Threonine and tyrosine kinase may serve as a prognostic biomarker for gallbladder cancer
Yuan Xie, Jian-Zhen Lin, An-Qiang Wang, Wei-Yu Xu, Jun-Yu Long, Yu-Feng Luo, Jie Shi, Zhi-Yong Liang, Xin-Ting Sang, Hai-Tao Zhao
World Journal of Gastroenterology.2017; 23(31): 5787. CrossRef
Multiple siRNA delivery against cell cycle and anti-apoptosis proteins using lipid-substituted polyethylenimine in triple-negative breast cancer and nonmalignant cells
Manoj B. Parmar, Bárbara E. Arteaga Ballesteros, Timothy Fu, Remant Bahadur K.C., Hamidreza Montazeri Aliabadi, Judith C. Hugh, Raimar Löbenberg, Hasan Uludağ
Journal of Biomedical Materials Research Part A.2016; 104(12): 3031. CrossRef
Novel Mps1 Kinase Inhibitors with Potent Antitumor Activity
Antje M. Wengner, Gerhard Siemeister, Marcus Koppitz, Volker Schulze, Dirk Kosemund, Ulrich Klar, Detlef Stoeckigt, Roland Neuhaus, Philip Lienau, Benjamin Bader, Stefan Prechtl, Marian Raschke, Anna-Lena Frisk, Oliver von Ahsen, Martin Michels, Bertolt K
Molecular Cancer Therapeutics.2016; 15(4): 583. CrossRef
Microsatellite instability detected in tumor-related genes in C57BL/6J mice with thymic lymphoma induced by N -methyl- N -nitrosourea
Shuangyue Zhang, Xueyun Huo, Zhenkun Li, Xiaohong Li, Wang Tang, Changlong Li, Meng Guo, Xiaoyan Du, Zhenwen Chen
Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis.2015; 782: 7. CrossRef
Ataxia‐telangiectasia‐mutated protein expression with microsatellite instability in gastric cancer as prognostic marker
Jin Won Kim, Seock‐Ah Im, Min A Kim, Hyun Jin Cho, Dae Won Lee, Kyung‐Hun Lee, Tae‐Yong Kim, Sae‐Won Han, Do‐Youn Oh, Hyuk‐Joon Lee, Tae‐You Kim, Han‐Kwang Yang, Woo Ho Kim, Yung‐Jue Bang
International Journal of Cancer.2014; 134(1): 72. CrossRef
Mitosis as an anti-cancer drug target
Anna-Leena Salmela, Marko J. Kallio
Chromosoma.2013; 122(5): 431. CrossRef
The MPS1 Family of Protein Kinases
Xuedong Liu, Mark Winey
Annual Review of Biochemistry.2012; 81(1): 561. CrossRef
Meta-analysis of gene expression microarrays with missing replicates
Fan Shi, Gad Abraham, Christopher Leckie, Izhak Haviv, Adam Kowalczyk
BMC Bioinformatics.2011;[Epub] CrossRef
Exome sequencing identifies frequent mutation of ARID1A in molecular subtypes of gastric cancer
Kai Wang, Junsuo Kan, Siu Tsan Yuen, Stephanie T Shi, Kent Man Chu, Simon Law, Tsun Leung Chan, Zhengyan Kan, Annie S Y Chan, Wai Yin Tsui, Siu Po Lee, Siu Lun Ho, Anthony K W Chan, Grace H W Cheng, Peter C Roberts, Paul A Rejto, Neil W Gibson, David J Po
Nature Genetics.2011; 43(12): 1219. CrossRef
High frequency of TTK mutations in microsatellite-unstable colorectal cancer and evaluation of their effect on spindle assembly checkpoint
Iina Niittymäki, Alexandra Gylfe, Leena Laine, Marko Laakso, Heli J. Lehtonen, Johanna Kondelin, Jaana Tolvanen, Kari Nousiainen, Jeroen Pouwels, Heikki Järvinen, Kyösti Nuorva, Jukka-Pekka Mecklin, Markus Mäkinen, Ari Ristimäki, Torben F. Ørntoft, Sampsa
Carcinogenesis.2011; 32(3): 305. CrossRef
Physiological Relevance of Cell Cycle Kinases
Marcos Malumbres
Physiological Reviews.2011; 91(3): 973. CrossRef

11,687 View
88 Download
20 Crossref

A Clinical Analysis of PTEN Expressions in Breast Cancers: Hang Ju Cho, Jeong Soo Kim, Kee Hwan Kim, Chang Hyeok Ahn, Woo Chan Park, Se Jeong Oh, Sang Seol Jung, Keun Woo Lim, Seock Ah Im; Cancer Res Treat. 2003;35(2):102-108. Published online April 30, 2003; DOI: https://doi.org/10.4143/crt.2003.35.2.102

Abstract PDF

PURPOSE
The PTEN gene, a novel tumor suppressor, is localized to chromosome 10q23.3 and shares extensive homology with the cytoskeletal protein, tensin. A high frequency of mutations at the PTEN locus has been described in a variety of neoplasms including breast cancer and Cowden Disease. However, the role of PTEN alterations and its association with clinicopathological factors have not been well established. We investigated the relationship between the PTEN expression and clinicopathological factors.
MATERIALS AND METHODS
Formalin-fixed, paraffin-embedded tissues from 105 women with breast cancer were evaluated for the PTEN expression and were scored semi-quantitatively based on staining intensity and distribution. Results were statistically compared with clinicopathological factors.
RESULTS
Forty-seven (45%) of the 105 breast cancers had a loss of the PTEN expression. In the recurrent group, 19 of 32 (59%) patients showed a loss of the PTEN expression, whereas in the non-recurrent group, only 28 of 73 (38%) patients showed a loss of the PTEN expression. The loss of PTEN expression correlated with estrogen receptors (ER) (p=0.027), recurrence (p=0.046), HER-2/neu overexpression (p=0.016), disease-free survival (p=0.0163), and overall survival (p=0.0357). In particular, when HER-2/ neu was overexpressed, the overall survival rate correlated with the loss of PTEN expression statistically (p=0.0454), whereas when HER-2/neu was negative, there was no correlation (p=0.9808). Progesterone receptor (PR) and disease stage had no relationship with the PTEN expression. CONCLUSION: Our results support that PTEN plays a role as a tumor suppressor in breast cancer and is a prognostic factor in predicting recurrence.

Citations

Citations to this article as recorded by

The prognostic value and potential drug target of phosphatase and tensin homolog in breast cancer patients
Feng Xu, Chao Zhang, Jianxiu Cui, Jun Liu, Jie Li, Hongchuan Jiang
Medicine.2017; 96(36): e8000. CrossRef

3,824 View
32 Download
1 Crossref

Clinical Analysis of PTEN, p53 and Her-2/neu Expressions in Thyroid Cancers: Jeong Soo Kim, Ja Seong Bae, Kee Hwan Kim, Chang Hyeok Ahn, Se Jeong Oh, Hae Myung Jeon, Keun Woo Lim, Chung Soo Chun; Cancer Res Treat. 2001;33(5):433-437. Published online October 31, 2001; DOI: https://doi.org/10.4143/crt.2001.33.5.433

Abstract PDF

PURPOSE
The dual-specificity phosphatase PTEN/ MMAC1/TEP1 has recently been identified as the tumor suppressor gene most frequently mutated and/or deleted in human tumors. However, PTEN mutations have rarely been detected in sporadic thyroid cancers. Therefore, this study investigated the PTEN expression of thyroid cancer and the relationship between PTEN, clinical status and other biologic factors such as HER-2/neu and p53.
MATERIALS AND METHODS
The study samples consisted of 62 thyroid cancer specimens and 24 benign thyroid tumor specimens from patients who were operated on the Department of Surgery, Uijongbu St. Mary's hospital during the 5 years from January 1995 until January 2000. All tumors were studied by immunohistochemical staining using monoclonal antibodies against PTEN, HER-2/neu and p53. The results were analyzed statistically.
RESULTS
PTEN protein was found to be under-expressed more frequently in thyroid cancers (29%) than in benign thyroid tumors (4.2%). The reduction in PTEN expression in thyroid cancers was not significantly related with the recorded clinical factors such as size, age, lymph node metastasis and p53, except for HER-2 which was found to be significantly related (p=0.001). HER-2 over- expression was noted in thyroid cancer (83.8%) more frequently than in benign tumors (16.7%).
CONCLUSION
This study has demonstrated that the under-expression of PTEN protein and the over-expression of HER-2 protein may play a role in the carcinogenesis and development of thyroid cancer.

Citations

Citations to this article as recorded by

Links between Breast and Thyroid Cancer: Hormones, Genetic Susceptibility and Medical Interventions
Man Lu, Hanqing Liu, Bilian Zheng, Shengrong Sun, Chuang Chen
Cancers.2022; 14(20): 5117. CrossRef
Recommendations on Surveillance for Differentiated Thyroid Carcinoma in Children with PTEN Hamartoma Tumor Syndrome
L.A. Jonker, C.A. Lebbink, M.C.J. Jongmans, R.A.J. Nievelstein, J.H.M. Merks, E.J.M. Nieveen van Dijkum, T.P. Links, N. Hoogerbrugge, A.S.P. van Trotsenburg, H.M. van Santen
European Thyroid Journal.2020; 9(5): 234. CrossRef
Activity of Green Tea Polyphenol Epigallocatechin-3-gallate Against Ovarian Carcinoma Cell Lines
Yong Wook Kim, Su Mi Bae, Joon Mo Lee, Sung Eun Namkoong, Sei Jun Han, Byoung Rai Lee, Insu P. Lee, Sang Hee Kim, Young Joo Lee, Chong Kook Kim, Yong-Wan Kim, Woong Shick Ahn
Cancer Research and Treatment.2004; 36(5): 315. CrossRef

4,462 View
33 Download
3 Crossref

Author index