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Synonymous mutation adenomatous polyposis coliΔ486s affects exon splicing and may predispose patients to adenomatous polyposis coli/mutY DNA glycosylase mutation‑negative familial adenomatous polyposis

  • Authors:
    • Wei Qing Liu
    • Jian Dong
    • Yan Xia Peng
    • Wen Liang Li
    • Jun Yang
  • View Affiliations / Copyright

    Affiliations: Department of Internal Medicine‑Oncology, First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan 650032, P.R. China, Department of Internal Medicine‑Oncology, Third Affiliated Hospital of Kunming Medical University, Kunming, Yunnan 650106, P.R. China, School of Forensic Medicine, Kunming Medical University, Kunming, Yunnan 650500, P.R. China, Department of Oncology, First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan 650032, P.R. China
    Copyright: © Liu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 4931-4939
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    Published online on: September 20, 2018
       https://doi.org/10.3892/mmr.2018.9495
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Abstract

Familial adenomatous polyposis (FAP) is an autosomal dominant‑inherited colorectal cancer. Recent advances in genetics have indicated that the majority of patients with FAP carry germline mutations of the adenomatous polyposis coli (APC) and mutY DNA glycosylase (MUTYH) genes. However, a large subset of families with a history of FAP have undetectable pathogenic alterations, termed APC/MUTYH mutation‑negative FAP. To investigate the germline mutations in the APC and MUTYH genes in Chinese patients with FAP, 13 unrelated patients were enrolled. Through genetic sequencing, four known pathogenic alterations (Lys1061LysfsTer2, Glu1309AspfsTer4, Arg283Ter and Ser1196Ter) of APC and two novel disease‑associated pathogenic mutations (Tyr152Ter and Ter522Gly) in MUTYH were identified in six individuals. For samples that did not present with pathogenic alterations, the functional effects of missense, synonymous and intronic mutations were analyzed using bioinformatics tools and databases. Bioinformatics prediction suggested that the synonymous mutation Tyr486Tyr in APC (APC∆486s) was likely a disease‑causing polymorphism and may have induced the exon skipping of APC. A hybrid mini‑gene assay was performed, which confirmed that the synonymous single nucleotide polymorphism APC∆486s induced major splicing defects with skipping of exon 12 in APC. The data of the present study suggested that the synonymous polymorphism APC∆486s was a potential pathogenic alteration that predisposed APC/MUTYH mutation‑negative patients to FAP.
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Copy and paste a formatted citation
Spandidos Publications style
Liu WQ, Dong J, Peng YX, Li WL and Yang J: Synonymous mutation adenomatous polyposis coliΔ486s affects exon splicing and may predispose patients to adenomatous polyposis coli/mutY DNA glycosylase mutation‑negative familial adenomatous polyposis. Mol Med Rep 18: 4931-4939, 2018.
APA
Liu, W.Q., Dong, J., Peng, Y.X., Li, W.L., & Yang, J. (2018). Synonymous mutation adenomatous polyposis coliΔ486s affects exon splicing and may predispose patients to adenomatous polyposis coli/mutY DNA glycosylase mutation‑negative familial adenomatous polyposis. Molecular Medicine Reports, 18, 4931-4939. https://doi.org/10.3892/mmr.2018.9495
MLA
Liu, W. Q., Dong, J., Peng, Y. X., Li, W. L., Yang, J."Synonymous mutation adenomatous polyposis coliΔ486s affects exon splicing and may predispose patients to adenomatous polyposis coli/mutY DNA glycosylase mutation‑negative familial adenomatous polyposis". Molecular Medicine Reports 18.6 (2018): 4931-4939.
Chicago
Liu, W. Q., Dong, J., Peng, Y. X., Li, W. L., Yang, J."Synonymous mutation adenomatous polyposis coliΔ486s affects exon splicing and may predispose patients to adenomatous polyposis coli/mutY DNA glycosylase mutation‑negative familial adenomatous polyposis". Molecular Medicine Reports 18, no. 6 (2018): 4931-4939. https://doi.org/10.3892/mmr.2018.9495
Copy and paste a formatted citation
x
Spandidos Publications style
Liu WQ, Dong J, Peng YX, Li WL and Yang J: Synonymous mutation adenomatous polyposis coliΔ486s affects exon splicing and may predispose patients to adenomatous polyposis coli/mutY DNA glycosylase mutation‑negative familial adenomatous polyposis. Mol Med Rep 18: 4931-4939, 2018.
APA
Liu, W.Q., Dong, J., Peng, Y.X., Li, W.L., & Yang, J. (2018). Synonymous mutation adenomatous polyposis coliΔ486s affects exon splicing and may predispose patients to adenomatous polyposis coli/mutY DNA glycosylase mutation‑negative familial adenomatous polyposis. Molecular Medicine Reports, 18, 4931-4939. https://doi.org/10.3892/mmr.2018.9495
MLA
Liu, W. Q., Dong, J., Peng, Y. X., Li, W. L., Yang, J."Synonymous mutation adenomatous polyposis coliΔ486s affects exon splicing and may predispose patients to adenomatous polyposis coli/mutY DNA glycosylase mutation‑negative familial adenomatous polyposis". Molecular Medicine Reports 18.6 (2018): 4931-4939.
Chicago
Liu, W. Q., Dong, J., Peng, Y. X., Li, W. L., Yang, J."Synonymous mutation adenomatous polyposis coliΔ486s affects exon splicing and may predispose patients to adenomatous polyposis coli/mutY DNA glycosylase mutation‑negative familial adenomatous polyposis". Molecular Medicine Reports 18, no. 6 (2018): 4931-4939. https://doi.org/10.3892/mmr.2018.9495
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