Abstract
Hereditary non-polyposis colorectal cancer (HNPCC) is an autosomal dominant tumour predisposition syndrome caused by germline mutations in mismatch repair (MMR) genes. In contrast to MLH1 and MSH2, germline mutations in MSH6 are associated with a milder and particularly variable phenotype. Based on the reported interaction of the MMR complex and the base excision repair protein MUTYH, it was hypothesised that MUTYH mutations serve as phenotypical modifiers in HNPCC families. Recently, a significantly higher frequency of heterozygosity for MUTYH mutations among MSH6 mutation carriers was reported. We examined 64 MSH6 mutation carriers (42 truncating mutations, 19 missense mutations and 3 silent mutations) of the German HNPCC Consortium for MUTYH mutations by sequencing the whole coding region of the gene. Monoallelic MUTYH mutations were identified in 2 of the 64 patients (3.1%), no biallelic MUTYH mutation carrier was found. The frequency of MUTYH mutations was not significantly higher than that in healthy controls, neither in the whole patient group (P=0.30) nor in different subgroups regarding mutation type. Our results do not support the association between MSH6 mutations and heterozygosity for MUTYH mutations.
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Acknowledgements
The work was supported by a multicentre grant from the German Cancer Aid (Deutsche Krebshilfe e.V. Bonn, project no. 70-2371 and 106244).
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Supplementary Information accompanies the paper on European Journal of Human Genetics website (http://www.nature.com/ejhg)
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The German HNPCC-Consortium consists of the following centres (in alphabetical order): clinical centres in Bochum (in addition to authors: F Brasch, JT Epplen, S Hahn, C Pox, S Stemmler, A Tannapfel and J Willert), Bonn (in addition to authors: S Uhlhaas, M Sengteller, W Friedl, N Friedrichs and R Buettner), Düsseldorf (in addition to authors: B Betz, T Goecke, G Möslein and C Poremba), Dresden (in addition to authors: DE Aust, F Balck, A Bier, R Höhl, FR Kreuz, SR Pistorius and J Plaschke), Heidelberg (in addition to authors: F Cremer, M Keller, P Kienle, HP Knaebel, M von Knebel-Doeberitz, U Mazitschek and M Tariverdian), München/Regensburg (in addition to authors: A Laner, B Schönfeld, E Holinski-Feder, H Vogelsang, R Langer, S Dechant and P Rümmele) and centre for documentation and biometry in Leipzig (in addition to authors: M Loeffler, M Herold, U Enders and J Schaefer).
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Steinke, V., Rahner, N., Morak, M. et al. No association between MUTYH and MSH6 germline mutations in 64 HNPCC patients. Eur J Hum Genet 16, 587–592 (2008). https://doi.org/10.1038/ejhg.2008.26
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DOI: https://doi.org/10.1038/ejhg.2008.26
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