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A study on MSH2 and MLH1 mutations in hereditary nonpolyposis colorectal cancer families from the Basque Country, describing four new germline mutations

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Abstract

Hereditary non-polyposis colorectal cancer (HNPCC) or Lynch syndrome underlies between 2 and 5% of all colorectal cancer. It is inherited as an autosomal dominant condition due to mutations in the mismatch repair genes. Fifty-four non-related index cases, 21 of them fulfilling Amsterdam criteria I or II, were studied. Ten (10/21 = 47.6%) different pathological mutations were found in this group, two of which had not previously been reported—one in MLH1 and the other in MSH2-. In the remaining patients, we also found another family with one of these new mutations, and four additional changes, two of which were also new—a pathological change in MSH2 and a second change of uncertain significance in MLH1-, while the other two changes had already been reported. Of all mutations, eight were found in MSH2 (8/15 = 53.3%) and seven in MLH1 (7/15 = 46.6%), suggesting a slightly greater involvement of MSH2 in HNPCC than MLH1 in our population, in contrast to the results reported by other authors.

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Abbreviations

MMR:

Mismatch repair

HNPCC:

Hereditary non-polyposis colorectal cancer

CRFC:

Colorectal cancer

InSIGHT database:

International society for gastrointestinal hereditary tumours

CSGE:

Conformational-sensitive gel electrophoresis

MLPA:

Multiple ligation probe amplification

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Acknowledgments

This work was supported by grants: (a) 200411060 from the Department of Health of the Basque Government and (b) BI0O7/CA/006 from Basque Foundation for Health Innovation and Research.

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Authors and Affiliations

  1. Laboratorio de Genética Molecular (Servicio de Bioquímica), Hospital de Cruces, Plaza de Cruces s/n., 48903, Barakaldo-Bizkaia, Spain

    Cristina Martínez-Bouzas, Elena Beristain, Noelia Viguera & Maria Isabel Tejada

  2. Servicio de Digestivo, Hospital de Cruces, Barakaldo-Bizkaia, Spain

    Enrique Ojembarrena

  3. Servicio de Cirugía General, Hospital de Txagorritxu, Vitoria-Gasteiz, Spain

    Jose Errasti

  4. Servicio de Oncologia Medica, InstitutoOncologico, San Sebastián-Donosti, Spain

    Karmele Mujika

Authors
  1. Cristina Martínez-Bouzas
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  2. Elena Beristain
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  3. Enrique Ojembarrena
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  4. Jose Errasti
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  5. Karmele Mujika
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  6. Noelia Viguera
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  7. Maria Isabel Tejada
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Correspondence to Cristina Martínez-Bouzas or Maria Isabel Tejada.

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Martínez-Bouzas, C., Beristain, E., Ojembarrena, E. et al. A study on MSH2 and MLH1 mutations in hereditary nonpolyposis colorectal cancer families from the Basque Country, describing four new germline mutations. Familial Cancer 8, 533–539 (2009). https://doi.org/10.1007/s10689-009-9283-3

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  • DOI: https://doi.org/10.1007/s10689-009-9283-3

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