Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Oncology Letters
      • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Biomedical Reports
      • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • Information for Authors
    • Information for Reviewers
    • Information for Librarians
    • Information for Advertisers
    • Conferences
  • Language Editing
Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • For Authors
    • For Reviewers
    • For Librarians
    • For Advertisers
    • Conferences
  • Language Editing
Login Register Submit
  • This site uses cookies
  • You can change your cookie settings at any time by following the instructions in our Cookie Policy. To find out more, you may read our Privacy Policy.

    I agree
Search articles by DOI, keyword, author or affiliation
Search
Advanced Search
presentation
Oncology Letters
Join Editorial Board Propose a Special Issue
Print ISSN: 1792-1074 Online ISSN: 1792-1082
Journal Cover
May-2018 Volume 15 Issue 5

Full Size Image

Sign up for eToc alerts
Recommend to Library

Journals

International Journal of Molecular Medicine

International Journal of Molecular Medicine

International Journal of Molecular Medicine is an international journal devoted to molecular mechanisms of human disease.

International Journal of Oncology

International Journal of Oncology

International Journal of Oncology is an international journal devoted to oncology research and cancer treatment.

Molecular Medicine Reports

Molecular Medicine Reports

Covers molecular medicine topics such as pharmacology, pathology, genetics, neuroscience, infectious diseases, molecular cardiology, and molecular surgery.

Oncology Reports

Oncology Reports

Oncology Reports is an international journal devoted to fundamental and applied research in Oncology.

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine is an international journal devoted to laboratory and clinical medicine.

Oncology Letters

Oncology Letters

Oncology Letters is an international journal devoted to Experimental and Clinical Oncology.

Biomedical Reports

Biomedical Reports

Explores a wide range of biological and medical fields, including pharmacology, genetics, microbiology, neuroscience, and molecular cardiology.

Molecular and Clinical Oncology

Molecular and Clinical Oncology

International journal addressing all aspects of oncology research, from tumorigenesis and oncogenes to chemotherapy and metastasis.

World Academy of Sciences Journal

World Academy of Sciences Journal

Multidisciplinary open-access journal spanning biochemistry, genetics, neuroscience, environmental health, and synthetic biology.

International Journal of Functional Nutrition

International Journal of Functional Nutrition

Open-access journal combining biochemistry, pharmacology, immunology, and genetics to advance health through functional nutrition.

International Journal of Epigenetics

International Journal of Epigenetics

Publishes open-access research on using epigenetics to advance understanding and treatment of human disease.

Medicine International

Medicine International

An International Open Access Journal Devoted to General Medicine.

Journal Cover
May-2018 Volume 15 Issue 5

Full Size Image

Sign up for eToc alerts
Recommend to Library

  • Article
  • Citations
    • Cite This Article
    • Download Citation
    • Create Citation Alert
    • Remove Citation Alert
    • Cited By
  • Similar Articles
    • Related Articles (in Spandidos Publications)
    • Similar Articles (Google Scholar)
    • Similar Articles (PubMed)
  • Download PDF
  • Download XML
  • View XML
Article Open Access

Analysis of human MutS homolog 2 missense mutations in patients with colorectal cancer

  • Authors:
    • Xiaomei Zhang
    • Senqing Chen
    • Jun Yu
    • Yuanying Zhang
    • Min Lv
    • Ming Zhu
  • View Affiliations / Copyright

    Affiliations: Department of Molecular Biology, Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, Nanjing Medical University Affiliated Cancer Hospital, Nanjing, Jiangsu 210009, P.R. China
    Copyright: © Zhang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 6275-6282
    |
    Published online on: March 2, 2018
       https://doi.org/10.3892/ol.2018.8161
  • Expand metrics +
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )
Cited By (CrossRef): 0 citations Loading Articles...

This article is mentioned in:



Abstract

Germline mutations of DNA mismatch repair gene human MutS homolog 2 (hMSH2) are associated with hereditary nonpolyposis colorectal cancer (HNPCC). A total of one‑third of these mutations are missense mutations. Several hMSH2 missense mutations have been identified in patients in East Asia, although their function has not been evaluated. In the present study, the role of ten hMSH2 missense mutations in the pathogenesis of colorectal cancer was examined. The hMSH2/hMSH6 protein interaction system was established using yeast two‑hybrid screening. Next, the missense mutations were analyzed for their ability to affect the protein interaction of hMSH2 with its partner hMSH6. Additionally, the Sorting Intolerant from Tolerant tool was applied to predict the effects of different amino acid substitutions. The results demonstrated that certain hMSH2 mutations (L173R and C199R) caused a significant functional change in the human hMutSα complex and were identified to be pathological mutations. The Y408C, D603Y, P696L and S703Y mutations partially affected interaction and partly affected the function of hMSH2. The remaining four variants, T8M, I169V, A370T and Q419K, may be non‑functional polymorphisms or could affect protein function through other molecular mechanisms. The present study evaluated the functional consequences of previously unknown missense mutations in hMSH2, and may contribute to improved clinical diagnosis and mutation screening of HNPCC.
View Figures

Figure 1

Figure 2

Figure 3

View References

1 

Brosens LA, Offerhaus GJ and Giardiello FM: Hereditary colorectal cancer: Genetics and screening. Surg Clin North Am. 95:1067–1080. 2015. View Article : Google Scholar : PubMed/NCBI

2 

Lynch HT and de la Chapelle A: Genetic susceptibility to non-polyposis colorectal cancer. J Med Genet. 36:801–818. 1999.PubMed/NCBI

3 

In SiGHT: InSiGHT variant databases. https://www.insight-group.org/variants/databases/June 29–2017

4 

Woods MO, Williams P, Careen A, Edwards L, Bartlett S, McLaughlin JR and Younghusband HB: A new variant database for mismatch repair genes associated with Lynch syndrome. Hum Mutat. 28:669–673. 2007. View Article : Google Scholar : PubMed/NCBI

5 

Peltomaki P and Vasen HF: Mutations predisposing to hereditary nonpolyposis colorectal cancer: Database and results of a collaborative study. The International Collaborative Group on Hereditary Nonpolyposis Colorectal Cancer. Gastroenterology. 113:1146–1158. 1997. View Article : Google Scholar : PubMed/NCBI

6 

Obmolova G, Ban C, Hsieh P and Yang W: Crystal structures of mismatch repair protein MutS and its complex with a substrate DNA. Nature. 407:703–710. 2000. View Article : Google Scholar : PubMed/NCBI

7 

Lamers MH, Perrakis A, Enzlin JH, Winterwerp HH, de Wind N and Sixma TK: The crystal structure of DNA mismatch repair protein MutS binding to a GxT mismatch. Nature. 407:711–717. 2000. View Article : Google Scholar : PubMed/NCBI

8 

Jiricny J: The multifaceted mismatch-repair system. Nat Rev Mol Cell Biol. 7:335–346. 2006. View Article : Google Scholar : PubMed/NCBI

9 

Geng H, Sakato M, DeRocco V, Yamane K, Du C, Erie DA, Hingorani M and Hsieh P: Biochemical analysis of the human mismatch repair proteins hMutSα MSH2(G674A)-MSH6 and MSH2-MSH6(T1219D). J Biol Chem. 287:9777–9791. 2012. View Article : Google Scholar : PubMed/NCBI

10 

Fan Y, Wang W, Zhu M, Zhou J, Peng J, Xu L, Hua Z, Gao X and Wang Y: Analysis of hMLH1 missense mutations in East Asian patients with suspected hereditary nonpolyposis colorectal cancer. Clin Cancer Res. 13:7515–7521. 2007. View Article : Google Scholar : PubMed/NCBI

11 

Wang XL, Yuan Y, Zhang SZ, Cai SR, Huang YQ, Jiang Q and Zheng S: Clinical and genetic characteristics of Chinese hereditary nonpolyposis colorectal cancer families. World J Gastroenterol. 12:4074–4077. 2006. View Article : Google Scholar : PubMed/NCBI

12 

Nomura S, Sugano K, Kashiwabara H, Taniguchi T, Fukayama N, Fujita S, Akasu T, Moriya Y, Ohhigashi S, Kakizoe T and Sekiya T: Enhanced detection of deleterious and other germline mutations of hMSH2 and hMLH1 in Japanese hereditary nonpolyposis colorectal cancer kindreds. Biochem Biophys Res Commun. 271:120–129. 2000. View Article : Google Scholar : PubMed/NCBI

13 

Fan Y, Liu X, Zhang H, Dai J, Zhang X, Zhu M, Gao X and Wang Y: Variations in exon 7 of the MSH2 gene and susceptibility to gastrointestinal cancer in a Chinese population. Cancer Genet Cytogenet. 170:121–128. 2006. View Article : Google Scholar : PubMed/NCBI

14 

Leung SY, Chan TL, Chung LP, Chan AS, Fan YW, Hung KN, Kwong WK, Ho JW and Yuen ST: Microsatellite instability and mutation of DNA mismatch repair genes in gliomas. Am J Pathol. 153:1181–1188. 1998. View Article : Google Scholar : PubMed/NCBI

15 

Tang R, Hsiung C, Wang JY, Lai CH, Chien HT, Chiu LL, Liu CT, Chen HH, Wang HM, Chen SX, et al: Germ line MLH1 and MSH2 mutations in Taiwanese Lynch syndrome families: Characterization of a founder genomic mutation in the MLH1 gene. Clin Genet. 75:334–345. 2009. View Article : Google Scholar : PubMed/NCBI

16 

Zhang Y, Liu X, Fan Y, Ding J, Xu A, Zhou X, Hu X, Zhu M, Zhang X, Li S, et al: Germline mutations and polymorphic variants in MMR, E-cadherin and MYH genes associated with familial gastric cancer in Jiangsu of China. Int J Cancer. 119:2592–2596. 2006. View Article : Google Scholar : PubMed/NCBI

17 

Yuen ST, Chan TL, Ho JW, Chan AS, Chung LP, Lam PW, Tse CW, Wyllie AH and Leung SY: Germline, somatic and epigenetic events underlying mismatch repair deficiency in colorectal and HNPCC-related cancers. Oncogene. 21:7585–7592. 2002. View Article : Google Scholar : PubMed/NCBI

18 

Jin HY, Yan HL, Song LH, Cui L, Ding YJ and Sun SH: Identification and functional analysis of a novel germ-line mutation in hMSH2 from a Chinese hereditary nonpolyposis colorectal cancer family. Acad J Sec Mil Med Univ. 26:888–891. 2005.(In Chinese).

19 

Ng PC and Henikoff S: Predicting deleterious amino acid substitutions. Genome Res. 11:863–874. 2001. View Article : Google Scholar : PubMed/NCBI

20 

Kumar P, Henikoff S and Ng PC: Predicting the effects of coding non-synonymous variants on protein function using the SIFT algorithm. Nat Protoc. 4:1073–1081. 2009. View Article : Google Scholar : PubMed/NCBI

21 

Vander Molen J, Frisse LM, Fullerton SM, Qian Y, Del Bosque-Plata L, Hudson RR and Di Rienzo A: Population genetics of CAPN10 and GPR35: Implications for the evolution of type 2 diabetes variants. Am J Hum Genet. 76:548–560. 2005. View Article : Google Scholar : PubMed/NCBI

22 

Nystrom-Lahti M, Perrera C, Raschle M, Panyushkina-Seiler E, Marra G, Curci A, Quaresima B, Costanzo F, D'Urso M, Venuta S and Jiricny J: Functional analysis of MLH1 mutations linked to hereditary nonpolyposis colon cancer. Genes Chromosomes Cancer. 33:160–167. 2002. View Article : Google Scholar : PubMed/NCBI

23 

Clark AB, Cook ME, Tran HT, Gordenin DA, Resnick MA and Kunkel TA: Functional analysis of human MutSalpha and MutSbeta complexes in yeast. Nucleic Acids Res. 27:736–742. 1999. View Article : Google Scholar : PubMed/NCBI

24 

Rodríguez-Negrete E, Bejarano ER and Castillo AG: Using the yeast two-hybrid system to identify protein-protein interactions. Methods Mol Biol. 1072:241–258. 2014. View Article : Google Scholar : PubMed/NCBI

25 

Zhu M, Fan YM, Zhu YB and Wang YP: Establishment of a hMSH2/hMSH6 protein interaction system and functional evaluation of hMSH2 gene missense mutations. Zhonghua Yi Xue Yi Chuan Xue Za Zhi. 30:559–564. 2013.(In Chinese). PubMed/NCBI

26 

Duraturo F, Liccardo R, Cavallo A, De Rosa M, Grosso M and Izzo P: Association of low-risk MSH3 and MSH2 variant alleles with Lynch syndrome: Probability of synergistic effects. Int J Cancer. 129:1643–1650. 2011. View Article : Google Scholar : PubMed/NCBI

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Zhang X, Chen S, Yu J, Zhang Y, Lv M and Zhu M: Analysis of human MutS homolog 2 missense mutations in patients with colorectal cancer. Oncol Lett 15: 6275-6282, 2018.
APA
Zhang, X., Chen, S., Yu, J., Zhang, Y., Lv, M., & Zhu, M. (2018). Analysis of human MutS homolog 2 missense mutations in patients with colorectal cancer. Oncology Letters, 15, 6275-6282. https://doi.org/10.3892/ol.2018.8161
MLA
Zhang, X., Chen, S., Yu, J., Zhang, Y., Lv, M., Zhu, M."Analysis of human MutS homolog 2 missense mutations in patients with colorectal cancer". Oncology Letters 15.5 (2018): 6275-6282.
Chicago
Zhang, X., Chen, S., Yu, J., Zhang, Y., Lv, M., Zhu, M."Analysis of human MutS homolog 2 missense mutations in patients with colorectal cancer". Oncology Letters 15, no. 5 (2018): 6275-6282. https://doi.org/10.3892/ol.2018.8161
Copy and paste a formatted citation
x
Spandidos Publications style
Zhang X, Chen S, Yu J, Zhang Y, Lv M and Zhu M: Analysis of human MutS homolog 2 missense mutations in patients with colorectal cancer. Oncol Lett 15: 6275-6282, 2018.
APA
Zhang, X., Chen, S., Yu, J., Zhang, Y., Lv, M., & Zhu, M. (2018). Analysis of human MutS homolog 2 missense mutations in patients with colorectal cancer. Oncology Letters, 15, 6275-6282. https://doi.org/10.3892/ol.2018.8161
MLA
Zhang, X., Chen, S., Yu, J., Zhang, Y., Lv, M., Zhu, M."Analysis of human MutS homolog 2 missense mutations in patients with colorectal cancer". Oncology Letters 15.5 (2018): 6275-6282.
Chicago
Zhang, X., Chen, S., Yu, J., Zhang, Y., Lv, M., Zhu, M."Analysis of human MutS homolog 2 missense mutations in patients with colorectal cancer". Oncology Letters 15, no. 5 (2018): 6275-6282. https://doi.org/10.3892/ol.2018.8161
Follow us
  • Twitter
  • LinkedIn
  • Facebook
About
  • Spandidos Publications
  • Careers
  • Cookie Policy
  • Privacy Policy
How can we help?
  • Help
  • Live Chat
  • Contact
  • Email to our Support Team