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MYH, OGG1, MTH1, and APC alterations involved in the colorectal tumorigenesis of Korean patients with multiple adenomas

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Abstract

This study was done to characterize base excision repair (BER) genes and adenomatous polyposis coli (APC) alterations in the tumorigenesis of multiple colorectal adenomas in Korean patients. In total, 217 adenomas (mean number = 10) and 117 cancers were available from 143 patients. The heterozygous genotype of OGG1 c.1-18G>T was closely associated with multiple adenoma families (P < 0.001), while MYH A359V mutation exhibited a tendency (P = 0.053). MYH R170G mutation was exclusively identified in one patient. The G:C>T:A transversion or attenuated familial adenomatous polyposis (AFAP) mutations of APC was identified in the specific genotypes of BER variants. Tubular adenomas or adenomas with none-to-mild dysplasia were significantly associated with polymorphic genotypes of OGG1 IVS4-15 and S326C. In addition, large and pedunculated adenomas were more frequent in patients with G:C>T:A transversion and AFAP mutations of APC, respectively. However, BER variants were not associated with mismatch repair or altered p53 protein expression. Conclusively, two novel mutations of MYH and a novel OGG1 polymorphism seemed to be associated with multiple colorectal adenomas in Korean families, differing from those in other ethnic groups. Some BER variants involved in specific APC mutations are associated with characteristics of histogenesis other than altered mismatch repair or p53 pathway.

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References

  1. 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:CT:A mutations in colorectal tumors. Nat Genet 30:227–232

    Article  PubMed  CAS  Google Scholar 

  2. Boiteux S, Radicella JP (2000) The human OGG1 gene: structure, functions, and its implication in the process of carcinogenesis. Arch Biochem Biophys 377:1–8

    Article  PubMed  CAS  Google Scholar 

  3. Burt RW, Leppert MF, Slattery ML, Samowitz WS, Spirio LN, Kerber RA, Kuwada SK, Neklason DW, Disario JA, Lyon E, Hughes JP, Chey WY, White RL (2004) Genetic testing and phenotype in a large kindred with attenuated familial adenomatous polyposis. Gastroenterology 127:444–451

    Article  PubMed  Google Scholar 

  4. Cheadle JP, Sampson JR (2003) Exposing the MYtH about base excision repair and human inherited disease. Hum Mol Genet 12:R159–R165

    Article  PubMed  CAS  Google Scholar 

  5. den Dunnen JT, Antonarakis SE (2000) Mutation nomenclature extensions and suggestions to describe complex mutations: a discussion. Hum Mutat 15:7–12

    Article  Google Scholar 

  6. Fagman H, Larsson F, Arvidsson Y, Meuller J, Nordling M, Martinsson T, Helmbrecht K, Brabant G, Nilsson M (2003) Nuclear accumulation of full-length and truncated adenomatous polyposis coli protein in tumor cells depends on proliferation. Oncogene 22:6013–6022

    Article  PubMed  CAS  Google Scholar 

  7. Farrington SM, Tenesa A, Barnetson R, Wiltshire A, Prendergast J, Porteous M, Campbell H, Dunlop MG (2005) Germline susceptibility to colorectal cancer due to base-excision repair gene defects. Am J Hum Genet 77:112–119

    Article  PubMed  CAS  Google Scholar 

  8. Fleischmann C, Peto J, Cheadle J, Shah B, Sampson J, Houlston RS (2004) Comprehensive analysis of the contribution of germline MYH variation to early-onset colorectal cancer. Int J Cancer 109:554–558

    Article  PubMed  CAS  Google Scholar 

  9. Gu Y, Parker A, Wilson TM, Bai H, Chang DY, Lu AL (2002) Human MutY homolog, a DNA glycosylase involved in base excision repair, physically and functionally interacts with mismatch repair proteins human MutS homolog 2/human MutS homolog 6. J Biol Chem 277:11135–11142

    Article  PubMed  CAS  Google Scholar 

  10. Hansen R, Saebo M, Skjelbred CF (2005) GPX Pro198Leu and OGG1 Ser326Cys polymorphisms and risk of development of colorectal adenomas and colorectal cancer. Cancer Lett 229:85–91

    Article  PubMed  CAS  Google Scholar 

  11. Janssen K, Schlink K, Gotte W, Hippler B, Kaina B, Oesch F (2001) DNA repair activity of 8-oxoguanine DNA glycosylase 1 (OGG1) in human lymphocytes is not dependent on genetic polymorphism Ser326/Cys326. Mutat Res 486:207–216

    PubMed  CAS  Google Scholar 

  12. Janssen KP, el-Marjou F, Pinto D, Sastre X, Rouillard D, Fouquet C, Soussi T, Louvard D, Robine S (2002) Targeted expression of oncogenic K-ras in intestinal epithelium causes spontaneous tumorigenesis in mice. Gastroenterology 123:492–504

    Article  PubMed  CAS  Google Scholar 

  13. 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 

  14. Kennedy CH, Cueto R, Belinsky SA, Lechner JF, Pryor WA (1998) Overexpression of hMTH1 mRNA: a molecular marker of oxidative stress in lung cancer cells. FEBS Lett 429:17–20

    Article  PubMed  CAS  Google Scholar 

  15. Kim IJ, Ku JL, Kang HC, Park JH, Yoon KA, Shin Y, Park HW, Jang SG, Lim SK, Han SY, Shin YK, Lee MR, Jeong SY, Shin HR, Lee JS, Kim WH, Park JG (2004) Mutational analysis of OGG1, MYH, MTH1 in FAP, HNPCC and sporadic colorectal cancer patients: R154H OGG1 polymorphism is associated with sporadic colorectal cancer patients. Hum Genet 115:498–503

    Article  PubMed  CAS  Google Scholar 

  16. Kim JC, Lee KH, Ka IH, Koo KH, Roh SA, Kim HC, Yu CS, Kim TW, Chang HM, Gong GY, Kim JS (2004) Characterization of mutator phenotype in familial colorectal cancer patients not fulfilling Amsterdam criteria. Clin Cancer Res 10:6159–6168

    Article  PubMed  CAS  Google Scholar 

  17. Knudsen AL, Marie Luise Bisgaard ML, Steffen Bülow S (2003) Attenuated familial adenomatous polyposis (AFAP). A review of the literature. Familial Cancer 2:43–55

    Article  PubMed  Google Scholar 

  18. Lamlum H, Al Tassan N, Jaeger E, Frayling I, Sieber O, Reza FB, Eckert M, Rowan A, Barclay E, Atkin W, Williams C, Gilbert J, Cheadle J, Bell J, Houlston R, Bodmer W, Sampson J, Tomlinson I (2000) Germline APC variants in patients with multiple colorectal adenomas, with evidence for the particular importance of E1317Q. Hum Mol Genet 9:2215–2221

    PubMed  CAS  Google Scholar 

  19. Miyaki M, Iijima T, Yamaguchi T (2005) Germline mutations of the MYH gene in Japanese patients with multiple colorectal adenomas. Mutat Res 578:430–433

    PubMed  CAS  Google Scholar 

  20. Miyoshi Y, Ando H, Nagase H, Nishisho I, Horii A, Miki Y, Mori T, Utsunomiya J, Baba S, Petersen G, Hamilton SR, Kinzler KW, Vogelstein B, Nakamura Y (1992) Germ-line mutations of the APC gene in 53 familial adenomatous polyposis patients. Proc Natl Acad Sci USA 89:4452–4456

    Article  PubMed  CAS  Google Scholar 

  21. Nagase H, Nakamura Y (1993) Mutations of the APC (adenomatous polyposis coli) gene. Hum Mutat 2:425–434

    Article  PubMed  CAS  Google Scholar 

  22. Nakabeppu Y (2001) Molecular genetics and structural biology of human MutT homolog, MTH1. Mutat Res 477:59–70

    PubMed  CAS  Google Scholar 

  23. Nohmi T, Kim SR, Yamada M (2005) Modulation of oxidative mutagenesis and carcinogenesis by polymorphic forms of human DNA repair enzymes. Mutat Res 591:60–73

    PubMed  CAS  Google Scholar 

  24. Parker AR, O’Meally RN, Sahin F, Su GH, Racke FK, Nelson WG, DeWeese TL, Eshleman JR (2003) Defective human MutY phosphorylation exists in colorectal cancer cell lines with wild-type MutY alleles. J Biol Chem 278:47937–47945

    Article  PubMed  CAS  Google Scholar 

  25. Peterlongo P, Mitra N, Chuai S, Kirchhoff T, Palmer C, Huang H, Nafa K, Offit K, Ellis NA (2005) Colorectal cancer risk in individuals with biallelic or monoallelic mutations of MYH. Int J Cancer 114:505–507

    Article  PubMed  CAS  Google Scholar 

  26. Rosin-Arbesfeld R, Townsley F, Bienz M (2000) The APC tumour suppressor has a nuclear export function. Nature 406:1009–1012

    Article  PubMed  CAS  Google Scholar 

  27. Salahshor S, Kressner U, Pahlman L, Glimelius B, Lindmark G, Lindblom A (1999) Colorectal cancer with and without microsatellite instability involves different genes. Genes Chromosomes Cancer 26:247–252

    Article  PubMed  CAS  Google Scholar 

  28. Sampson JR, Dolwani S, Jones S, Eccles D, Ellis A, Evans DG, Frayling I, Jordan S, Maher ER, Mak T, Maynard J, Pigatto F, Shaw J, Cheadle JP (2003) Autosomal recessive colorectal adenomatous polyposis due to inherited mutations of MYH. Lancet 362:39–41

    Article  PubMed  CAS  Google Scholar 

  29. Shinmura K, Yamaguchi S, Saitoh T, Kohno T, Yokota J (2001) Somatic mutations and single nucleotide polymorphisms of base excision repair genes involved in the repair of 8-hydroxyguanine in damaged DNA. Cancer Lett 166:65–69

    Article  PubMed  CAS  Google Scholar 

  30. Sieber OM, Lipton L, Crabtree M, Heinimann K, Fidalgo P, Phillips RK, Bisgaard ML, Orntoft TF, Aaltonen LA, Hodgson SV, Thomas HJ, Tomlinson IP (2003) Multiple colorectal adenomas, classic adenomatous polyposis, and germ-line mutations in MYH. N Engl J Med 348:791–799

    Article  PubMed  Google Scholar 

  31. Sieber OM, Segditsas S, Knudsen AL, Zhang J, Luz J, Rowan AJ, Spain SL, Thirlwell C, Howarth KM, Jaeger EE, Robinson J, Volikos E, Silver A, Kelly G, Aretz S, Frayling I, Hutter P, Dunlop M, Guenther T, Neale K, Phillips R, Heinimann K, Tomlinson IP (2006) Disease severity and genetic pathways in attenuated familial adenomatous polyposis vary greatly, but depend on the site of the germline mutation. Gut 55:1440–1448

    Article  PubMed  CAS  Google Scholar 

  32. Vasen HF (2000) Clinical diagnosis and management of hereditary colorectal cancer syndromes. J Clin Oncol 18:S81–S92

    Google Scholar 

  33. Venesio T, Molatore S, Cattaneo F, Arrigoni A, Risio M, Ranzani GN (2004) High frequency of MYH gene mutations in a subset of patients with familial adenomatous polyposis. Gastroenterology 126:1681–1685

    Article  PubMed  CAS  Google Scholar 

  34. 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 

  35. Wheeler JM (2005) Epigenetics, mismatch repair genes and colorectal cancer. Ann R Coll Surg Engl 87:15–20

    Article  PubMed  CAS  Google Scholar 

  36. Yamane A, Kohno T, Ito K, Sunaga N, Aoki K, Yoshimura K, Murakami H, Nojima Y, Yokota J (2004) Differential ability of polymorphic OGG1 proteins to suppress mutagenesis induced by 8-hydroxyguanine in human cell in vivo. Carcinogenesis 25:1689–1694

    Article  PubMed  CAS  Google Scholar 

  37. Yoshimura K, Hanaoka T, Ohnami S, Ohnami S, Kohno T, Liu Y, Yoshida T, Sakamoto H, Tsugane S (2003) Allele frequencies of single nucleotide polymorphisms (SNPs) in 40 candidate genes for gene-environment studies on cancer: data from population-based Japanese random samples. J Hum Genet 48:654–658

    Article  PubMed  Google Scholar 

  38. Zhou XL, Eriksson U, Werelius B, Kressner U, Sun XF, Lindblom A (2004) Definition of candidate low risk APC alleles in a Swedish population. Int J Cancer 110:550–557

    Article  PubMed  CAS  Google Scholar 

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Acknowledgement

This study was supported from the Basic Research Program of the Korea Science and Engineering Foundation (grant no. R01-2006-000-10021-0).

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Authors and Affiliations

  1. Department of Surgery, University of Ulsan College of Medicine, Seoul, South Korea

    Jin C. Kim, In H. Ka, Yoo M. Lee, Kum H. Koo, Hee C. Kim & Chang S. Yu

  2. Laboratory of Cancer Biology and Genetics, Asan Institute for Life Sciences, 388-1 Poongnap-2-Dong Songpa-Ku, Seoul, South Korea

    Jin C. Kim, In H. Ka, Yoo M. Lee, Kum H. Koo, Hee C. Kim, Chang S. Yu & Se J. Jang

  3. Department of Pathology, University of Ulsan College of Medicine, Seoul, South Korea

    Se J. Jang

  4. Division of Molecular Therapeutics, Korean Research Institute of Bioscience and Biotechnology, Daejeon, South Korea

    Yong S. Kim

  5. Department of Surgery, Catholic University of Daegu, Daegu, South Korea

    Han I. Lee

  6. Department of Surgery, Hanyang University Hospital, Seoul, South Korea

    Kang H. Lee

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  1. Jin C. Kim
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Correspondence to Jin C. Kim.

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Kim, J.C., Ka, I.H., Lee, Y.M. et al. MYH, OGG1, MTH1, and APC alterations involved in the colorectal tumorigenesis of Korean patients with multiple adenomas. Virchows Arch 450, 311–319 (2007). https://doi.org/10.1007/s00428-006-0363-6

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  • DOI: https://doi.org/10.1007/s00428-006-0363-6

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