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MLH1 and MSH2 mutation screening in HNPCC families of Hungary - Two new MMR gene mutations.
Eur J Surg Oncol. 2014 Nov; 40(11):1445-52.EJ

Abstract

INTRODUCTION

Hereditary Non-Polyposis Colorectal Cancer is an inherited disease with deleterious germline mutations in the DNA mismatch repair genes causing the development of colon cancer and other malignancies. This is the first study in Hungary screening the population of our colorectal cancer patients in order to identify the prevalence of the disease.

METHODS

In families who met the Modified Amsterdam and Bethesda Criteria the removed tumor tissue was first examined by immunohistochemistry and microsatellite instability analysis. Those cases which showed high microsatellite instability underwent DNA sequencing and multiple ligation dependent probe amplification.

RESULTS

Of the 1576 patients with colorectal cancer underwent screening for the modified Amsterdam and Bethesda criteria, 69 (4.4%) and 166 (10.5%) fulfilled the criteria respectively. 15 patients (31%) of the Amsterdam positive group and 19 patients from the Bethesda positive (18.1%) were MSI-H. There were 8 pathogenic mutations identified in 9 families (60%) in the Amsterdam positive group. 5 mutations were found in 5 families (26%) in the Bethesda positive group. 12 pathogenic mutations were identified, two of these are newly identified, and being published first in this work. These two new mutations were located on MLH1 (g.31276_35231del) and MSH2 (c.969_970delTC) genes.

CONCLUSION

The prevalence of the mutations in the MLH1 and MSH2 genes was almost equal in our Hungarian colorectal cancer patients. One mutation in the MLH1 gene (c.143A > C; p.Q48P) was identified in three different families. Whether this mutation is the most frequent in the Hungarian population is still unidentified and warrant further investigation.

Authors+Show Affiliations

Institute of Surgery, University of Debrecen, Medical and Health Science Centre, Debrecen, Hungary. Electronic address: mtanyi@hotmal.com.Department of Pathogenetics, National Institute of Oncology, Budapest, Hungary.Department of Obstetrics and Gynecology, Division of Gynecological Oncology, University of Pennsylvania, Philadelphia, USA.Pathological Department, University of Debrecen, Medical and Health Science Center, Debrecen, Hungary.Department of Clinical Biochemistry and Molecular Pathology, University of Debrecen, Medical and Health Science Center, Debrecen, Hungary.Institute of Internal Medicine, University of Debrecen, Medical and Health Science Centre, Hungary.Institute of Internal Medicine, University of Debrecen, Medical and Health Science Centre, Hungary.Institute of Internal Medicine, University of Debrecen, Medical and Health Science Centre, Hungary.Oncological Department, University of Debrecen, Medical and Health Science Center, Debrecen, Hungary.Department of Radio-Oncology, University of Debrecen, Medical and Health Science Centre, Debrecen, Hungary.Institute of Surgery, University of Debrecen, Medical and Health Science Centre, Debrecen, Hungary.Department of Pathogenetics, National Institute of Oncology, Budapest, Hungary.Institute of Surgery, University of Debrecen, Medical and Health Science Centre, Debrecen, Hungary.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

25107687

Citation

Tanyi, M, et al. "MLH1 and MSH2 Mutation Screening in HNPCC Families of Hungary - Two New MMR Gene Mutations." European Journal of Surgical Oncology : the Journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology, vol. 40, no. 11, 2014, pp. 1445-52.
Tanyi M, Olasz J, Tanyi JL, et al. MLH1 and MSH2 mutation screening in HNPCC families of Hungary - Two new MMR gene mutations. Eur J Surg Oncol. 2014;40(11):1445-52.
Tanyi, M., Olasz, J., Tanyi, J. L., Tóth, L., Antal-Szalmás, P., Ress, Z., Bubán, T., Palatka, K., András, C., Urbancsek, H., Garami, Z., Csuka, O., & Damjanovich, L. (2014). MLH1 and MSH2 mutation screening in HNPCC families of Hungary - Two new MMR gene mutations. European Journal of Surgical Oncology : the Journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology, 40(11), 1445-52. https://doi.org/10.1016/j.ejso.2014.07.032
Tanyi M, et al. MLH1 and MSH2 Mutation Screening in HNPCC Families of Hungary - Two New MMR Gene Mutations. Eur J Surg Oncol. 2014;40(11):1445-52. PubMed PMID: 25107687.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - MLH1 and MSH2 mutation screening in HNPCC families of Hungary - Two new MMR gene mutations. AU - Tanyi,M, AU - Olasz,J, AU - Tanyi,J L, AU - Tóth,L, AU - Antal-Szalmás,P, AU - Ress,Z, AU - Bubán,T, AU - Palatka,K, AU - András,C, AU - Urbancsek,H, AU - Garami,Z, AU - Csuka,O, AU - Damjanovich,L, Y1 - 2014/07/24/ PY - 2013/09/20/received PY - 2014/06/03/revised PY - 2014/07/11/accepted PY - 2014/8/10/entrez PY - 2014/8/12/pubmed PY - 2015/1/21/medline KW - Bethesda criteria KW - Hereditary Non-Polyposis Colorectal Cancer KW - MLH1 KW - MSH2 KW - Modified Amsterdam criteria SP - 1445 EP - 52 JF - European journal of surgical oncology : the journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology JO - Eur J Surg Oncol VL - 40 IS - 11 N2 - INTRODUCTION: Hereditary Non-Polyposis Colorectal Cancer is an inherited disease with deleterious germline mutations in the DNA mismatch repair genes causing the development of colon cancer and other malignancies. This is the first study in Hungary screening the population of our colorectal cancer patients in order to identify the prevalence of the disease. METHODS: In families who met the Modified Amsterdam and Bethesda Criteria the removed tumor tissue was first examined by immunohistochemistry and microsatellite instability analysis. Those cases which showed high microsatellite instability underwent DNA sequencing and multiple ligation dependent probe amplification. RESULTS: Of the 1576 patients with colorectal cancer underwent screening for the modified Amsterdam and Bethesda criteria, 69 (4.4%) and 166 (10.5%) fulfilled the criteria respectively. 15 patients (31%) of the Amsterdam positive group and 19 patients from the Bethesda positive (18.1%) were MSI-H. There were 8 pathogenic mutations identified in 9 families (60%) in the Amsterdam positive group. 5 mutations were found in 5 families (26%) in the Bethesda positive group. 12 pathogenic mutations were identified, two of these are newly identified, and being published first in this work. These two new mutations were located on MLH1 (g.31276_35231del) and MSH2 (c.969_970delTC) genes. CONCLUSION: The prevalence of the mutations in the MLH1 and MSH2 genes was almost equal in our Hungarian colorectal cancer patients. One mutation in the MLH1 gene (c.143A > C; p.Q48P) was identified in three different families. Whether this mutation is the most frequent in the Hungarian population is still unidentified and warrant further investigation. SN - 1532-2157 UR - https://www.unboundmedicine.com/medline/citation/25107687/MLH1_and_MSH2_mutation_screening_in_HNPCC_families_of_Hungary___Two_new_MMR_gene_mutations_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0748-7983(14)00538-1 DB - PRIME DP - Unbound Medicine ER -