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Assessment of microsatellite instability in head and neck cancer using consensus markers

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Abstract

Head and neck cancer is the sixth most common cancer in the world and one of the most lethal cancers. Microsatellite instability is an important characteristic of tumor cells and is observed both in presence and absence of mismatch repair gene mutations. The importance of microsatellite instability in head and neck cancer is not well established due to the lack of a consensus panel and selection of different markers, criteria and methodological variances. The main objective of this study was to investigate the performance of a consensus panel of microsatellite repeats by automated fragment analysis. Matched tumor and normal tissue samples from 99 patients were analyzed using five mononucleotide markers. Following PCR the amplified fragments were analyzed by capillary electrophoresis on an ABI 310 genetic analyzer. Microsatellite instability was observed in 26 patients. In 17 patients instability was detected at multiple loci. NR21 and BAT25 were the most frequently altered targets. These two mononucleotide markers could detect all samples displaying high-instability. In this study we describe a standardized fluorescent multiplex PCR combined with computerized analysis, which allows rapid and accurate analysis of a high number of samples and obviates the need to compare tumors with matching normal tissue.

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References

  1. Parkin DM, Bray F, Ferlay J, Pisani P (2005) Global cancer statistics, 2002. CA Cancer J Clin 55:74–108

    Article  PubMed  Google Scholar 

  2. Worsham MJ, Chen KM, Meduri V, Nygren AOH, Errami A, Schouten JP, Benninger MS (2006) Epigenetic events of disease progression in head and neck squamous cell carcinoma. Arch Otolaryngol Head Neck Surg 132:668–677

    Article  PubMed  Google Scholar 

  3. Sasiadek MM, Stembalska-Kozlowska A, Smigiel R, Ramsey D, Kayademir T, Blin N (2004) Impairment of MLH1 and CDKN2A in oncogenesis of laryngeal cancer. Br J Cancer 90:1594–1599

    Article  CAS  PubMed  Google Scholar 

  4. Anacleto C, Leopoldino AM, Rossi B, Soares FA, Lopez A, Rocha JC, Caballero O, Camargo AA, Simpson AJ, Pena SD (2005) Colorectal cancer “methylator phenotype”: fact or artifact? Neoplasia 7:331–335

    Article  CAS  PubMed  Google Scholar 

  5. Ellegren H (2004) Microsatellites: simple sequences with complex evolution. Nat Rev Genet 5:435–446

    Article  CAS  PubMed  Google Scholar 

  6. Demokan S, Suoglu Y, Demir D, Gozeler M, Dalay N (2006) Microsatellite instability and methylation of the DNA mismatch repair genes in head and neck cancer. Ann Oncol 17:995–999

    Article  CAS  PubMed  Google Scholar 

  7. Eshleman JR, Markowitz SD (1995) Microsatellite instability in inherited and sporadic neoplasms. Curr Opin Oncol 7:83–89

    CAS  PubMed  Google Scholar 

  8. Blacher JW, Flanagan LA, Smalley RL, Nassif NA, Burgart LJ, Halberg RB, Magid WM, Thibodau SN (2004) Development of fluorescent multiplex assay for detection of MSI-high tumors. Dis Markers 20:237–250

    Google Scholar 

  9. Blons H, Cabelguenne A, Carnot F, Laccourreye O, de Vaziers I, Hamelin R, Brasnu D, Beaune P, Laurent-Puig P (1999) Microsatellite analysis and response to chemotherapy in head and neck squamous cell carcinoma. Int J Cancer 84:410–415

    Article  CAS  PubMed  Google Scholar 

  10. Lin SC, Chang MF, Chung MY, Chang CS, Kao SY, Liu CJ, Chang KW (2005) Frequent microsatellite alterations of chromosome locus 4q13.1 in oral squamous cell carcinomas. J Oral Pathol Med 34:209–213

    Article  CAS  PubMed  Google Scholar 

  11. Morifuji M, Hiyama E, Murakami Y, Imamura Y, Sueda T, Yakoyama T (2003) Fluorescent-based BAT-26 analysis for distinct screening of microsatellite instability in colorectal cancers. Int J Oncol 22:807–813

    CAS  PubMed  Google Scholar 

  12. Maehara Y, Oda S, Sugimachi K (2001) The instability within: problems in current analyses of microsatellite instability. Mutat Res 461:249–263

    CAS  PubMed  Google Scholar 

  13. De Schutter H, Spaepen M, Van Opstal S, Poorten VV, Verbeken E, Nuyts S (2009) The prevalence of microsatellite instability in head and neck squamous cell carcinoma. J Cancer Res Clin Oncol 135:485–490

    Article  PubMed  Google Scholar 

  14. Boland CR, Thibodeau SN, Hamilton SR, Sidransky D, Eshleman JR, Burt RW, Meltzer SJ, Rodriguez-Bigas MA, Fodde R, Ranzani GN, Srivastava S (1998) 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 58:5248–5257

    CAS  PubMed  Google Scholar 

  15. Umar A, Boland CR, Terdiman JP, Syngal S, de la Chapelle A, Rüschoff J, Fishel R, Lindor NM, Burgart LJ, Hamelin R, Hamilton SR, Hiatt RA, Jass J, Lindblom A, Lynch HT, Peltomaki P, Ramsey SD, Rodriguez-Bigas MA, Vasen HF, Hawk ET, Barrett JC, Freedman AN, Srivastava S (2004) Revised Bethesda Guidelines for hereditary nonpolyposis colorectal cancer (Lynch syndrome) and microsatellite instability. J Natl Cancer Inst 96:261–268

    Article  CAS  PubMed  Google Scholar 

  16. Ferreira AM, Westers H, Wu Y, Niessen RC, Olderode-Berends M, van der Sluis T, van der Zee AG, Hollema H, Kleibeuker JH, Sijmons RH, Hofstra RM (2009) Do microsatellite instability profiles really differ between colorectal and endometrial tumors? Genes Chromosom Cancer 48:552–557

    Article  CAS  PubMed  Google Scholar 

  17. De Schutter H, Spaepen M, Mc Bride WH, Nuyts S (2007) The clinical relevance of microsatellite alterations in head and neck squamous cell carcinoma: a critical review. Eur J Hum Genet 15:734–741

    Article  PubMed  Google Scholar 

  18. Suraweera N, Duval A, Reperant M, Vaury C, Furlan D, Leroy K, Seruca R, Iacopetta B, Hamelin R (2002) Evaluation of tumor microsatellite instability using five quasimonomorphic mononucleotide repeats and pentaplex PCR. Gastroenterology 123:1804–1811

    Article  CAS  PubMed  Google Scholar 

  19. Murphy KM, Zhang S, Geiger T, Hafez MJ, Bacher J, Berg KD, Eshleman JR (2006) Comparison of the microsatellite instability analysis system and the Bethesda Panel for the detection of microsatellite instability in colorectal cancers. J Mol Diagn 830:5–311

    Google Scholar 

  20. Wang YF, Cheung TH, Lo KWK, Yim SF, Chan LKY, Buhard O, Duval A, Chung TKH, Hamelin R (2006) Detection of microsatellite instability in endometrial cancer: advantages of a panel of five mononucleotide repeats over the National Cancer Institute panel of markers. Carcinogenesis 27:951–955

    Article  Google Scholar 

  21. Buhard O, Suraweera N, Lectard A, Duval A, Hamelin R (2004) Quasimonomorphic mononucleotide repeats for high level microsatellite instability analysis. Dis Markers 20:251–257

    PubMed  Google Scholar 

  22. Uryu H, Oda Y, Shiratsuchi H, Oda S, Yamamoto H, Komune S, Tsuneyoshi M (2005) Microsatellite instability and proliferating activity in sinonasal cacinoma: molecular genetic and immunohistochemical comparison with oral squamous cell carcinoma. Oncol Rep 14:1133–1142

    CAS  PubMed  Google Scholar 

  23. Miyazato H, Tomita S, Tamai O, Isa T, Shiraishi M, Kusano T, Muto Y, Koja S (1999) Microsatellite instability in double cancers of the esophagus and head and neck. Dis Esophagus 12:132–136

    Article  CAS  PubMed  Google Scholar 

  24. Abou-Elhamd KE, Habib TN, Moussa AE, Badawy BS (2008) The role of genetic susceptibility in head and neck squamous cell carcinoma. Eur Arch Otorhinolaryngol 265:217–222

    Article  PubMed  Google Scholar 

  25. Zhigang H, Demin H, Han G, Erzhong F, Xiaohong C, Hongbo X (2007) Significance and mechanism of microsatellite instability in laryngeal squamous cell carcinoma. Otolaryngol 36:168–174

    Google Scholar 

  26. Kubo N, Yashiro M, Ohira M, Hori T, Fujiwara I, Hirakawa K (2005) Frequent microsatellite instability in primary esophageal carcinoma associated with extraesophageal primary carcinoma. Int J Cancer 114:166–173

    Article  CAS  PubMed  Google Scholar 

  27. Xicola RM, Llor X, Pons E, Castells A, Alenda C, Pinol V, Andreu M, Castellvi-Bel S, Jover R, Bessa X, Giros A, Duque JM, Nicolas-Perez D, Rigau J, Gassull MA (2007) Performance of different microsatellite marker panels for detection of mismatch repair-deficient colorectal tumors. J Natl Cancer Inst 99:244–252

    Article  CAS  PubMed  Google Scholar 

  28. Deschoolmeester V, Baay M, Wuyts W, Marck EV, Damme NV, Vermeulen P, Lukaszuk K, Lardon F, Vermorken JB (2008) Detection of microsatellite instability in colorectal cancer using an alternative multplex assay of quasi-monomorphic mononucleotide markers. J Mol Diagn 10:154–159

    Article  CAS  PubMed  Google Scholar 

  29. Koy S, Plaschke J, Luksch H, Friedrich K, Kuhlisch E, Eckelt U, Martinez R (2008) Microsatellite instability and loss of heterozygosity in suqmous cell carcinoma of the head and neck. Head Neck 30:1105–1113

    Article  PubMed  Google Scholar 

  30. Field JK, Klaris H, Howard P, Vaughan ED, Spandidos DA, Jones AS (1995) Microsatellite instability in squamous cell carcinoma of the head and neck. Br J Cancer 71:1065–1069

    CAS  PubMed  Google Scholar 

  31. Rozanska-Kudelska M, Walenczak I, Pepinski W, Sieskiewicz A, Skawronska M, Rogowski M (2008) Evaluation of tumor microsatellite instability in larygeal cancer using five quasimonomorphic mononucleotide repeats and pentaplex PCR. Adv Med Sci 53:59–63

    Article  CAS  PubMed  Google Scholar 

  32. Partridge M, Emilion G, Pateromichelakis S, A’Hern R, Phillips E, Langdon J (1998) Allelic imbalance of chromosomal loci implicated in the pathogenesis of oral precancer, cumulative loss and its relationship with progression to cancer. Oral Oncol 34:77–83

    Article  CAS  PubMed  Google Scholar 

  33. Ha PK, Pilkington TA, Westra WH, Sciubba J, Sidransky D, Califano JA (2002) Progression of microsatellite instability from premalignant lesions to tumors of the head and neck. Int J Cancer 102:615–617

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Basic Oncology, I.U. Oncology Institute, 34093, Capa, Istanbul, Turkey

    Zubeyde Yalniz, Semra Demokan & Nejat Dalay

  2. Department of Otolaryngology, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey

    Yusufhan Suoglu & Murat Ulusan

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  1. Zubeyde Yalniz
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  2. Semra Demokan
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  3. Yusufhan Suoglu
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  4. Murat Ulusan
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  5. Nejat Dalay
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Correspondence to Nejat Dalay.

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Yalniz, Z., Demokan, S., Suoglu, Y. et al. Assessment of microsatellite instability in head and neck cancer using consensus markers. Mol Biol Rep 37, 3541–3545 (2010). https://doi.org/10.1007/s11033-010-0001-x

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  • DOI: https://doi.org/10.1007/s11033-010-0001-x

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