Colorectal Cancer
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World J Gastroenterol. Feb 28, 2006; 12(8): 1192-1197
Published online Feb 28, 2006. doi: 10.3748/wjg.v12.i8.1192
Pedigree and genetic analysis of a novel mutation carrier patient suffering from hereditary nonpolyposis colorectal cancer
Miklós Tanyi, Judith Olasz, Géza Lukács, Orsolya Csuka, László Tóth, Zoltán Szentirmay, Zsuzsa Ress, Zsolt Barta, János L Tanyi, László Damjanovich
Miklós Tanyi, Géza Lukács, László Damjanovich, 1st Department of Surgery, University of Debrecen, Medical and Health Sciences Center, Debrecen, Hungary
Judith Olasz, Orsolya Csuka, Department of Pathogenetics, National Institute of Oncology, Budapest, Hungary
László Tóth, Department of Pathology, University of Debrecen, Medical and Health Sciences Center, Debrecen, Hungary
Zoltán Szentirmay, Department of Human and Experimental Tumor Pathology, National Institute of Oncology, Budapest, Hungary
Zsuzsa Ress, Zsolt Barta, 3rd Department of Medicine, University of Debrecen, Medical and Health Sciences Center, Debrecen, Hungary
János L Tanyi, Department of Obstetrics and Gynecology, Baylor College of Medicine, Houston, TX, United States
Author contributions: All authors contributed equally to the work.
Correspondence to: Miklós Tanyi, MD, 1st Department of Surgery, Medical and Health Sciences Center, University of Debrecen, H-4012 Debrecen, Nagyerdei krt. 98, PO Box 27,Hungary.
Telephone: +36-52-418033 Fax: +36-52-415517
Received: October 2, 2005
Revised: October 25, 2005
Accepted: November 10, 2005
Published online: February 28, 2006

AIM: To screen a suspected Hungarian HNPCC family to find specific mutations and to evaluate their effect on the presentation of the disease.

METHODS: The family was identified by applying the Amsterdam and Bethesda Criteria. Immunohistochemistry was performed, and DNA samples isolated from tumor tissue were evaluated for microsatellite instability. The identification of possible mutations was carried out by sequencing the hMLH1 and hMSH2 genes.

RESULTS: Two different mutations were observed in the index patient and in his family members. The first mutation was located in exon 7, codon 422 of hMSH2, and caused a change from Glu to STOP codon. No other report of such a mutation has been published, as far as we could find in the international databases. The second mutation was found in exon 3 codon 127 of the hMSH2 gene, resulting in Asp→Ser substitution. The second mutation was already published, as a non-pathogenic allelic variation.

CONCLUSION: The pedigree analysis suggested that the newly detected nonsense mutation in exon 7 of the hMSH2 gene might be responsible for the development of colon cancers. In family members where the exon 7 mutation is not coupled with this missense mutation, colon cancer appears after the age of 40. The association of these two mutations seems to decrease the age of manifestation of the disease into the early thirties.

Keywords: Hereditary nonpolyposis colon cancer, Bethesda criteria, Mutation, hMLH1, hMSH2