MT1XT20 Single Quasi-Monomorphic Mononucleotide Marker for Detection of Microsatellite Instability in Iranian Patients with Hereditary Nonpolyposis Colorectal Cancer (HNPCC)

Document Type : Original Article (s)

Authors

1 MSc Student, Department of Genetics and Molecular Biology, School of Medicine AND Student Research Committee, Isfahan University of Medical Sciences, Isfahan, Iran

2 Assistant Professor, Department of Genetics and Molecular Biology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran

3 Associate Professor, Poursina Hakim Gastrointestinal Research Center, Poursina Hakim Research Institution AND Isfahan University of Medical Sciences, Isfahan, Iran

4 Professor, Cellular and Molecular Research Center, Shahrekord University of Medical Sciences, Shahrekord, Iran

5 PhD Student, Cellular and Molecular Research Center, Shahrekord University of Medical Sciences, Shahrekord, Iran

6 Associate Professor, Department of Genetics and Molecular Biology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran

Abstract

Background: Colorectal malignancies with high microsatellite instability (MSI-H), either hereditary or sporadic, demonstrate better prognosis, altered response to fluorouracil (5FU) chemotherapy and altered operative approach. It is now recommended to perform MSI testing for all new cases of colorectal cancers regardless of being categorized as hereditary or sporadic. This study aimed to evaluate MT1XT20 mononucleotide marker in Iranian patients with hereditary nonpolyposis colorectal cancer (HNPCC). The samples were further characterized using Promega five-marker MSI testing panel and immunohistochemical (IHC) technique.Methods: MT1XT20 mononucleotide marker and commercially available kit (Promega, USA) incorporating five quasi-monomorphic markers were studied in 20 cases of HNPCC using polymerase chain reaction (PCR) technique. IHC was performed to evaluate the status of all four important mismatch repair (MMR) proteins, too.Findings: Eight (40%), seven (35%) and five (25%) cases showed MSI using Promega kit, IHC and MT1XT20, respectively. Among the markers included in Promega kit, BAT26 marker with instability in all 8 samples (100%) was the most instable marker. NR24 and NR21 markers showed instability in 7 cases (87.5%); BAT25 and MONO 27 markers were instable in 6 (75.0%) and 5 (62.5%) specimens, respectively.Conclusion: Although MT1XT20 is considered as a valid single marker in Italian population, it seems this is not hold true about the Iranian patients. Instead, BAT26 among the markers included in Promega MSI testing was shown instability in all 8 samples of MSI-H colorectal cancer (CRC). Therefore, it may be concluded that BAT26 alone is as efficient as the cohort of five markers in Iranian patients.

Keywords


  1. Lynch HT, Boland CR, Gong G, Shaw TG, Lynch PM, Fodde R, et al. Phenotypic and genotypic heterogeneity in the Lynch syndrome: diagnostic, surveillance and management implications. Eur J Hum Genet 2006; 14(4): 390-402.
  2. Zeinalian M, Emami MH, Salehi R, Naimi A, Kazemi M, Hashemzadeh-Chaleshtori M. Molecular analysis of Iranian colorectal cancer patients at risk for Lynch syndrome: a new molecular, clinicopathological feature. J Gastrointest Cancer 2015; 46(2): 118-25.
  3. Boland CR. The mystery of mismatch repair deficiency: lynch or lynch-like? Gastroenterology 2013; 144(5): 868-70.
  4. Ionov Y, Peinado MA, Malkhosyan S, Shibata D, Perucho M. Ubiquitous somatic mutations in simple repeated sequences reveal a new mechanism for colonic carcinogenesis. Nature 1993; 363(6429): 558-61.
  5. Thibodeau SN, French AJ, Roche PC, Cunningham JM, Tester DJ, Lindor NM, et al. Altered expression of hMSH2 and hMLH1 in tumors with microsatellite instability and genetic alterations in mismatch repair genes. Cancer Res 1996; 56(21): 4836-40.
  6. Chaksangchaichot P, Punyarit P, Petmitr S. Novel hMSH2, hMSH6 and hMLH1 gene mutations and microsatellite instability in sporadic colorectal cancer. J Cancer Res Clin Oncol 2007; 133(1): 65-70.
  7. Tautz D. Hypervariability of simple sequences as a general source for polymorphic DNA markers. Nucleic Acids Res 1989; 17(16): 6463-71.
  8. Lynch HT, de la Chapelle A. Hereditary colorectal cancer. N Engl J Med 2003; 348(10): 919-32.
  9. Fukutomi Y, Moriwaki H, Nagase S, Tajika M, Naito T, Miwa Y, et al. Metachronous colon tumors: risk factors and rationale for the surveillance colonoscopy after initial polypectomy. J Cancer Res Clin Oncol 2002; 128(10): 569-74.
  10. Deschoolmeester V, Baay M, Wuyts W, Van Marck E, Van Damme N, Vermeulen P, et al. Detection of microsatellite instability in colorectal cancer using an alternative multiplex assay of quasi-monomorphic mononucleotide markers. J Mol Diagn 2008; 10(2): 154-9.
  11. Ribic CM, Sargent DJ, Moore MJ, Thibodeau SN, French AJ, Goldberg RM, et al. Tumor microsatellite-instability status as a predictor of benefit from fluorouracil-based adjuvant chemotherapy for colon cancer. N Engl J Med 2003; 349(3): 247-57.
  12. Rodriguez-Bigas MA, Moeslein G. Surgical treatment of hereditary nonpolyposis colorectal cancer (HNPCC, Lynch syndrome). Fam Cancer 2013; 12(2): 295-300.
  13. Shia J. Immunohistochemistry versus microsatellite instability testing for screening colorectal cancer patients at risk for hereditary nonpolyposis colorectal cancer syndrome. Part I. The utility of immunohistochemistry. J Mol Diagn 2008; 10(4): 293-300.
  14. Ward R, Meldrum C, Williams R, Mokany E, Scott R, Turner J, et al. Impact of microsatellite testing and mismatch repair protein expression on the clinical interpretation of genetic testing in hereditary non-polyposis colorectal cancer. J Cancer Res Clin Oncol 2002; 128(8): 403-11.
  15. Boland CR, Thibodeau SN, Hamilton SR, Sidransky D, Eshleman JR, Burt RW, et al. A National Cancer Institute Workshop on Microsatellite Instability for cancer detection and familial predisposition: development of international criteria for the determination of microsatellite instability in colorectal cancer. Cancer Res 1998; 58(22): 5248-57.
  16. Bacher JW, Flanagan LA, Smalley RL, Nassif NA, Burgart LJ, Halberg RB, et al. Development of a fluorescent multiplex assay for detection of MSI-High tumors. Dis Markers 2004; 20(4-5): 237-50.
  17. Umar A, Boland CR, Terdiman JP, Syngal S, de la Chapelle A, Ruschoff J, et al. Revised Bethesda Guidelines for hereditary nonpolyposis colorectal cancer (Lynch syndrome) and microsatellite instability. J Natl Cancer Inst 2004; 96(4): 261-8.
  18. Vasen HF, Watson P, Mecklin JP, Lynch HT. New clinical criteria for hereditary nonpolyposis colorectal cancer (HNPCC, Lynch syndrome) proposed by the International Collaborative group on HNPCC. Gastroenterology 1999; 116(6): 1453-6.
  19. Patil DT, Bronner MP, Portier BP, Fraser CR, Plesec TP, Liu X. A five-marker panel in a multiplex PCR accurately detects microsatellite instability-high colorectal tumors without control DNA. Diagn Mol Pathol 2012; 21(3): 127-33.
  20. Buhard O, Cattaneo F, Wong YF, Yim SF, Friedman E, Flejou JF, et al. Multipopulation analysis of polymorphisms in five mononucleotide repeats used to determine the microsatellite instability status of human tumors. J Clin Oncol 2006; 24(2): 241-51.
  21. Xicola RM, Llor X, Pons E, Castells A, Alenda C, Pinol V, et al. Performance of different microsatellite marker panels for detection of mismatch repair-deficient colorectal tumors. J Natl Cancer Inst 2007; 99(3): 244-52.
  22. de la Chapelle A. Microsatellite instability phenotype of tumors: genotyping or immunohistochemistry? The jury is still out. J Clin Oncol 2002; 20(4): 897-9.
  23. Woerner SM, Gebert J, Yuan YP, Sutter C, Ridder R, Bork P, et al. Systematic identification of genes with coding microsatellites mutated in DNA mismatch repair-deficient cancer cells. Int J Cancer 2001; 93(1): 12-9.
  24. Findeisen P, Kloor M, Merx S, Sutter C, Woerner SM, Dostmann N, et al. T25 repeat in the 3' untranslated region of the CASP2 gene: a sensitive and specific marker for microsatellite instability in colorectal cancer. Cancer Res 2005; 65(18): 8072-8.
  25. Bianchi F, Galizia E, Catalani R, Belvederesi L, Ferretti C, Corradini F, et al. CAT25 is a mononucleotide marker to identify HNPCC patients. J Mol Diagn 2009; 11(3): 248-52.
  26. Morandi L, de Biase D, Visani M, Monzoni A, Tosi A, Brulatti M, et al. T([20]) repeat in the 3'-untranslated region of the MT1X gene: a marker with high sensitivity and specificity to detect microsatellite instability in colorectal cancer. Int J Colorectal Dis 2012; 27(5): 647-56.
  27. Pikor LA, Enfield KS, Cameron H, Lam WL. DNA extraction from paraffin embedded material for genetic and epigenetic analyses. J Vis Exp 2011; (49).
  28. Nemati A, Rahmatabadi ZK, Fatemi A, Emami MH. Hereditary nonpolyposis colorectal cancer and familial colorectal cancer in Central part of Iran, Isfahan. J Res Med Sci 2012; 17(1): 67-73.
  29. Fishel R. Signaling mismatch repair in cancer. Nat Med 1999; 5(11): 1239-41.
  30. Boland CR, Goel A. Microsatellite instability in colorectal cancer. Gastroenterology 2010; 138(6): 2073-87.
  31. Lindor NM, Burgart LJ, Leontovich O, Goldberg RM, Cunningham JM, Sargent DJ, et al. Immunohistochemistry versus microsatellite instability testing in phenotyping colorectal tumors. J Clin Oncol 2002; 20(4): 1043-8.
  32. Bouzourene H, Taminelli L, Chaubert P, Monnerat C, Seelentag W, Sandmeier D, et al. A cost-effective algorithm for hereditary nonpolyposis colorectal cancer detection. Am J Clin Pathol 2006; 125(6): 823-31.
  33. Brennetot C, Buhard O, Jourdan F, Flejou JF, Duval A, Hamelin R. Mononucleotide repeats BAT-26 and BAT-25 accurately detect MSI-H tumors and predict tumor content: implications for population screening. Int J Cancer 2005; 113(3): 446-50.
  34. Haghighi MM, Javadi GR, Parivar K, Milanizadeh S, Zali N, Fatemi SR, et al. Frequent MSI mononucleotide markers for diagnosis of hereditary nonpolyposis colorectal cancer. Asian Pac J Cancer Prev 2010; 11(4): 1033-5.
  35. Ichikawa A, Sugano K, Fujita S. DNA variants of BAT-25 in Japanese, a locus frequently used for analysis of microsatellite instability. Jpn J Clin Oncol 2001; 31(7): 346-8.
  36. Esemuede I, Forslund A, Khan SA, Qin LX, Gimbel MI, Nash GM, et al. Improved testing for microsatellite instability in colorectal cancer using a simplified 3-marker assay. Ann Surg Oncol 2010; 17(12): 3370-8.
  37. Esmailnia G, Montazer-Haghighi M, Javadi Gh, Parivar K, Zali M. Microsatellite instability markers status in colorectal cancer. Zahedan J Res Med Sci 2014; 16(2): 25-8.
  38. Shemirani AI, Haghighi MM, Zadeh SM, Fatemi SR, Taleghani MY, Zali N, et al. Simplified MSI marker panel for diagnosis of colorectal cancer. Asian Pac J Cancer Prev 2011; 12(8): 2101-4.