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MYH Y165C and G382D mutations in hepatocellular carcinoma and cholangiocarcinoma patients

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Abstract

Purpose: Production of reactive oxygen species (ROS) during chronic inflammation has been implicated in the progression of liver diseases and carcinogenesis. Subjects with inflammatory liver disease and one non-functional allele of the base excision repair gene, MYH, may be more susceptible to progression to cancer due to MYH haploinsufficiency in repairing oxidative damage caused by ROS. Here, we investigated the association of two common germline MYH mutations in patients with hepatocellular carcinoma (HCC) and cholangiocarcinoma. Methods: DNA from patients with HCC (n=48) or cholangiocarcinoma (n=84) compared to non-cancerous controls (n=308) were genotyped for the Y165C and G382D mutations in MYH. Results: There was no significant difference in MYH mutation carrier status between patients with HCC (1/48), cholangiocarcinoma (3/84), and non-cancerous controls (4/308). Conclusions: Patients with HCC or cholangiocarcinoma do not have an increased incidence of monoallelic MYH mutations pre-disposing them to disease.

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References

  • Akyerli CB, Ozbek U, Aydin-Sayitoglu M, Sirma S, Ozcelik T (2003) Analysis of MYH Tyr165Cys and Gly382Asp variants in childhood leukemias. J Cancer Res Clin Oncol 129:604–605

    Article  PubMed  Google Scholar 

  • Al-Tassan N, Chmiel NH, Maynard J, Fleming N, Livingston AL, Williams GT, Hodges AK, Davies DR, David SS, Sampson JR, Cheadle JP (2002) Inherited variants of MYH associated with somatic G:C→T:A mutations in colorectal tumors. Nat Genet 30:227–232

    Article  PubMed  CAS  Google Scholar 

  • Al-Tassan N, Eisen T, Maynard J, Bridle H, Shah B, Fleischmann C, Sampson JR, Cheadle JP, Houlston RS (2004) Inherited variants in MYH are unlikely to contribute to the risk of lung carcinoma. Hum Genet 114:207–210

    Article  PubMed  Google Scholar 

  • Chmiel NH, Livingston AL, David SS (2003) Insight into the functional consequences of inherited variants of the hMYH adenine glycosylase associated with colorectal cancer: complementation assays with hMYH variants and pre-steady-state kinetics of the corresponding mutated E. coli enzymes. J Mol Biol 327:431–443

    Article  PubMed  CAS  Google Scholar 

  • Farinati F, Cardin R, Degan P, De Maria N, Floyd RA, Van Thiel DH, Naccarato R (1999) Oxidative DNA damage in circulating leukocytes occurs as an early event in chronic HCV infection. Free Radic Biol Med 27:1284–1291

    Article  PubMed  CAS  Google Scholar 

  • Guan Y, Manuel RC, Arvai AS, Parikh SS, Mol CD, Miller JH, Lloyd S, Tainer JA (1998) MutY catalytic core, mutant and bound adenine structures define specificity for DNA repair enzyme superfamily. Nat Struct Biol 5:1058–1064

    Article  PubMed  CAS  Google Scholar 

  • Ichiba M, Maeta Y, Mukoyama T, Saeki T, Yasui S, Kanbe T, Okano J, Tanabe Y, Hirooka Y, Yamada S, Kurimasa A, Murawaki Y, Shiota G (2003) Expression of 8-hydroxy-2′-deoxyguanosine in chronic liver disease and hepatocellular carcinoma. Liver Int 23:338–345

    Article  PubMed  CAS  Google Scholar 

  • Jaiswal M, LaRusso NF, Shapiro RA, Billiar TR, Gores GJ (2001) Nitric oxide-mediated inhibition of DNA repair potentiates oxidative DNA damage in cholangiocytes. Gastroenterology 120:190–199

    Article  PubMed  CAS  Google Scholar 

  • Jones S, Emmerson P, Maynard J, Best JM, Jordan S, Williams GT, Sampson JR, Cheadle JP (2002) Biallelic germline mutations in MYH predispose to multiple colorectal adenoma and somatic G:C→T:A mutations. Hum Mol Genet 11:2961–2967

    Article  PubMed  CAS  Google Scholar 

  • Kambara T, Whitehall VL, Spring KJ, Barker MA, Arnold S, Wynter CV, Matsubara N, Tanaka N, Young JP, Leggett BA, Jass JR (2004) Role of inherited defects of MYH in the development of sporadic colorectal cancer. Genes Chromosomes Cancer 40:1–9

    Article  PubMed  CAS  Google Scholar 

  • Kim CJ, Cho YG, Park CH, Kim SY, Nam SW, Lee SH, Yoo NJ, Lee JY, Park WS (2004) Genetic alterations of the MYH gene in gastric cancer. Oncogene 23:6820–6822

    Article  PubMed  CAS  Google Scholar 

  • Kitada T, Seki S, Iwai S, Yamada T, Sakaguchi H, Wakasa K (2001) In situ detection of oxidative DNA damage, 8-hydroxydeoxyguanosine, in chronic human liver disease. J Hepatol 35:613–618

    Article  PubMed  CAS  Google Scholar 

  • Loguercio C, Federico A (2003) Oxidative stress in viral and alcoholic hepatitis. Free Radic Biol Med 34:1–10

    Article  PubMed  CAS  Google Scholar 

  • Moriya M, Grollman AP (1993) Mutations in the mutY gene of Escherichia coli enhance the frequency of targeted G:C→T:A transversions induced by a single 8-oxoguanine residue in single-stranded DNA. Mol Gen Genet 239:72–76

    PubMed  CAS  Google Scholar 

  • Nghiem Y, Cabrera M, Cupples CG, Miller JH (1988) The mutY gene: a mutator locus in Escherichia coli that generates G.C–T.A transversions. Proc Natl Acad Sci USA 85:2709–2713

    Article  PubMed  CAS  Google Scholar 

  • Ohshima H, Bartsch H (1994) Chronic infections and inflammatory processes as cancer risk factors: possible role of nitric oxide in carcinogenesis. Mutat Res 305:253–264

    PubMed  CAS  Google Scholar 

  • Sakakura C, Hagiwara A, Taniguchi H, Yamaguchi T, Yamagishi H, Takahashi T, Koyama K, Nakamura Y, Abe T, Inazawa J (1999) Chromosomal aberrations in human hepatocellular carcinomas associated with hepatitis C virus infection detected by comparative genomic hybridization. Br J Cancer 80:2034–2039

    Article  PubMed  CAS  Google Scholar 

  • Seki S, Kitada T, Sakaguchi H, Nakatani K, Wakasa K (2003) Pathological significance of oxidative cellular damage in human alcoholic liver disease. Histopathology 42:365–371

    Article  PubMed  CAS  Google Scholar 

  • Shibutani S, Takeshita M, Grollman AP (1991) Insertion of specific bases during DNA synthesis past the oxidation-damaged base 8-oxodG. Nature 349:431–434

    Article  PubMed  CAS  Google Scholar 

  • Shimoda R, Nagashima M, Sakamoto M, Yamaguchi N, Hirohashi S, Yokota J, Kasai H (1994) Increased formation of oxidative DNA damage, 8-hydroxydeoxyguanosine, in human livers with chronic hepatitis. Cancer Res 54:3171–3172

    PubMed  CAS  Google Scholar 

  • Wang L, Baudhuin LM, Boardman LA, Steenblock KJ, Petersen GM, Halling KC, French AJ, Johnson RA, Burgart LJ, Rabe K, Lindor NM, Thibodeau SN (2004) MYH mutations in patients with attenuated and classic polyposis and with young-onset colorectal cancer without polyps. Gastroenterology 127:9–16

    Article  PubMed  CAS  Google Scholar 

  • Wang XW, Hussain SP, Huo TI, Wu CG, Forgues M, Hofseth LJ, Brechot C, Harris CC (2002) Molecular pathogenesis of human hepatocellular carcinoma. Toxicology 181–182:43–47

    Article  PubMed  Google Scholar 

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Correspondence to W. Edward Highsmith.

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Financial Support: Grants CA82862 and CA100882 from the National Institutes of Health, a Harold Amos Medical Faculty Development Award from The Robert Wood Johnson Foundation, and from the Miles and Shirley Fiterman Center for Digestive Diseases at the Mayo Clinic, Rochester, MN (to L. Roberts).

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Baudhuin, L.M., Roberts, L.R., Enders, F.T. et al. MYH Y165C and G382D mutations in hepatocellular carcinoma and cholangiocarcinoma patients. J Cancer Res Clin Oncol 132, 159–162 (2006). https://doi.org/10.1007/s00432-005-0056-6

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  • DOI: https://doi.org/10.1007/s00432-005-0056-6

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