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Q48P mutation in the hMLH1 gene associated with Lynch syndrome in three Hungarian families

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Abstract

Lynch syndrome (Hereditary nonpolyposis colorectal cancer, HNPCC) is an inherited disease with variable phenotype causing the development of colon cancer and other malignancies. The basis of the disease is believed to be the mismatch repair gene mutations. Genetic screening has been performed among the patients who have undergone surgery for colon cancer at the University of Debrecen, Department of Surgery. Tumor samples of the screened patients were submitted to immunohistochemistry on hMLH1, hMSH2 and hMSH6 genes, microsatellite instability testing, followed by sequencing and multiple ligation dependent probe amplification. Three families were identified with the missense mutation c.143A>C (p.Q48P) of hMLH1 gene. In one of the families a segregation analysis of this particular variant was also accomplished. The segregation analysis revealed a clear correlation between the tumor cases and the occurrence of this mutation. However, none of the analyzed 100 healthy controls demonstrated the same aberration. There is only one published evidence in the literature about the presence of this rare variant in any population. The Gln to Pro switch in the ATPase domain, a conservative region of the hMLH1 gene, creates significant changes in the protein structure. These results indicate that this mutation is the abnormality responsible for the patients’ phenotype and it is feasible that this particular aberration occurs more frequently among Hungarian Lynch syndrome patients.

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Fig. 1
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Abbreviations

HNPCC:

Hereditary nonpolyposis colorectal cancer

MLPA:

Multiple ligation dependent probe amplification

MMR:

Mismatch repair

MSI:

Microsatellite instability

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Authors and Affiliations

  1. Department of Surgery, Medical and Health Science Centre, University of Debrecen, Móricz Zs. Krt. 22, 4032, Debrecen, Hungary

    Miklós Tanyi, Zoltán Garami & László Damjanovich

  2. Department of Pathogenetics, National Institute of Oncology, Budapest, Hungary

    Judit Olasz & Orsolya Csuka

  3. Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Perelman Center for Advanced Medicine, University of Pennsylvania Health System, West Pavilion, 3rd Floor, 3400 Civic Center Boulevard, Philadelphia, PA, 19104, USA

    Janos L. Tanyi

  4. Pathological Department, Medical and Health Science Centre, University of Debrecen, Debrecen, Hungary

    László Tóth

  5. Department of Clinical Biochemistry and Molecular Pathology, Medical and Health Science Centre, University of Debrecen, Debrecen, Hungary

    Péter Antal-Szalmás

  6. 1st Department of Internal Medicine, Medical and Health Science Centre, University of Debrecen, Debrecen, Hungary

    Tamás Bubán

  7. Oncological Department, Medical and Health Science Centre, University of Debrecen, Debrecen, Hungary

    Csilla András

  8. Department of Radio-Oncology, Medical and Health Science Centre, University of Debrecen, Debrecen, Hungary

    Hilda Urbancsek

Authors
  1. Miklós Tanyi
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  2. Judit Olasz
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  3. Janos L. Tanyi
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  4. László Tóth
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  5. Péter Antal-Szalmás
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  6. Tamás Bubán
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  7. Csilla András
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  8. Hilda Urbancsek
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  9. Zoltán Garami
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  10. Orsolya Csuka
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  11. László Damjanovich
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Corresponding author

Correspondence to Miklós Tanyi.

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Tanyi, M., Olasz, J., Tanyi, J.L. et al. Q48P mutation in the hMLH1 gene associated with Lynch syndrome in three Hungarian families. Familial Cancer 11, 519–524 (2012). https://doi.org/10.1007/s10689-012-9515-9

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  • DOI: https://doi.org/10.1007/s10689-012-9515-9

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