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Single oligoarray-based detection of specific M918T mutation in RET oncogene in multiple endocrine neoplasia type 2B

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Abstract

The most important mutation associated with Multiple Endocrine Neoplasia type 2B (MEN 2B) is the change of thymine to cytosine in codon 918 of exon 16 in the RET oncogene (ATG → ACG). The aim of this work was to develop a single oligoarray by using tandem hybridization to detect the T918C/RET mutation for MEN 2B patients. Two genetically non-related families were studied; each family had a member affected by MEN2B. Both patients presented the T918C/RET mutation in a heterozygous fashion. None of the relatives was positive for this mutation; thus, these cases arose de novo. The proper mutation was confirmed by with different tools, PCR-Fok I endonuclease, direct sequencing, and also using our oligoarray. In this case, it is suitable to use a DNA target smaller than 150 bases with single- or double-stranded DNA and short probes of 7-mer. It was also possible to detect the mutation by employing different sources of DNA, fresh or paraffin-embedded tissues. Therefore, the present oligoarray can identify the most common M918T mutation of RET oncogene from a variety of DNA sources with good specificity and be a good alternative in the molecular diagnosis for MEN 2B cases.

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References

  1. Lodish, MB, Stratakis CA (2008) RET oncogene in MEN2, MEN2B, MTC, and other forms of thyroid cancer: molecular genetics and therapeutic advances. Expert Rev Anticancer Ther 8(4): 625–632

    Google Scholar 

  2. Eng C, Mulligan LM (1997) Mutations of the RET proto-oncogene in the multiple endocrine neoplasia type 2 syndromes, related sporadic tumours, and hirschsprung disease. Hum Mutat 9(2):97–109

    Article  PubMed  CAS  Google Scholar 

  3. Raue F, Frank-Raue K (2009) Genotype-phenotype relationship in multiple endocrine neoplasia type 2. Implications for clinical management. Hormones 8(1):23–28

    PubMed  Google Scholar 

  4. Mulligan LM, Ponder BA (1995) Genetic basis of endocrine disease: multiple endocrine neoplasia type 2. J Clin Endocrinol Metab 80(7):1989–1995

    Article  PubMed  CAS  Google Scholar 

  5. Hidalgo A, Medrano ME, Rodriguez S, Franco C, Martinez I, Benitez L, Salcedo M (1998) Presence of the 918 mutation in the RET proto-oncogene in a Mexican patient with multiple endocrine neoplasia type 2B. J Exp Clin Cancer Res 17(2):149–152

    PubMed  CAS  Google Scholar 

  6. Siegelman M, Mohabeer A, Fahey TJ III, Tomlinson G, Mayambala C, Jafari S, Noll WW, Thibodeau SN, Dawson DB (1997) Rapid, nonradioactive screening for mutations in exons 10, 11, and 16 of the RET protooncogene associated with inherited medullary thyroid carcinoma. Clin Chem 43(3):453–457

    PubMed  CAS  Google Scholar 

  7. Takahashi M, Asai N, Iwashita T, Murakami H, Ito S (1998) Mechanisms of development of multiple endocrine neoplasia type 2 and Hirschsprung’s disease by ret mutations. Recent Results Cancer Res 154:229–236

    PubMed  CAS  Google Scholar 

  8. Maldonado R, Barrera O, Colin C, Salcedo M, Gonzalez B, Espinoza M, Tenorio A, Beattie K (2003) Genosensor design for RET oncogene mutations related to medullary thyroid carcinoma. Mol Biotechnol 25(2):113–129

    Article  Google Scholar 

  9. Rangel-Lopez A, Maldonado-Rodriguez R, Salcedo-Varagas M, Espinosa-Lara JM, Méndez-Tenorio A, Beattie KL (2005) Low density DNA microarray for detection of most frequent TP53 missense point mutations. BMC Biotechnol 5(1):8

    Article  PubMed  Google Scholar 

  10. Mendoza-Lorenzo P, Maldonado R, Pacheco R, Méndez A, Piña-Sánchez P, Rangel A, Vazquez-Ortíz G, Salcedo M (2007) An oligoarray for the detection of human papillomavirus type 16 variants. Int J Gynecol Cancer 17(5):1083–1091

    Article  PubMed  CAS  Google Scholar 

  11. Bolino A, Schuffenecker I, Luo Y, Seri M, Silengo M, Tocco T, Chabrier G, Houdent C, Murat A, Schlumberger M, Tourniaire J, Lenoir GM, Romeo G (1995) RET mutations in exons 13 and 14 FMTC patients. Oncogene 10(12):2415–2419

    PubMed  CAS  Google Scholar 

  12. Mulligan LM, Marsh DJ, Robinson BG, Schuffenecker I, Zedenius J, Lips CJM, Gagel RF, Takai SI, Noll WW, Fink M, Raue F, Lacroix A, Thibodeau SN, Frilling A, Ponder BAJ, Eng C, for the International RET Mutation Consortium (1995) Genotype-phenotype correlation in multiple endocrine neoplasia type 2: report of the RET Mutation Consortium. J Intern Med 238(4):343–346

  13. González B, Salcedo M, Medrano ME, Mantilla A, Quiñónez G, Benítez-Bribiesca L, Rodríguez-Cuevas S, Cabrera L, de León B, Altamirano N, Tapia J, Dawson B (2003) RET oncogene mutations in medullary thyroid carcinoma in Mexican families. Arch Med Res 34(1):41–49

    Article  PubMed  Google Scholar 

  14. Rossel M, Schuffenecker I, Schlumberger M, Bonnardel C, Modigliani E, Gardet P, Navarro J, Luo Y, Romeo G, Lenoir G et al (1995) Detection of a germline mutation at codon 918 of the RET proto-oncogene in French MEN 2B families. Hum Genet 95(4):403–406

    Article  PubMed  CAS  Google Scholar 

  15. Yershov G, Barsky V, Belgovskiy A, Kirillov E, Kreindlin E, Ivanov I, Parinov S, Guschin D, Drobishev A, Dubiley S, Mirzabekov A (1996) DNA analysis and diagnostics on oligonucleotide microchips. Proc Natl Acad Sci USA 93(10):4913–4918

    Article  PubMed  CAS  Google Scholar 

  16. Mahadevappa M, Warrington JA (1999) A high-density probe array sample preparation method using 10- to 100-fold fewer cells. Nat Biotechnol 17(11):1134–1136

    Article  PubMed  CAS  Google Scholar 

  17. Maldonado-Rodriguez R, Espinosa-Lara M, Loyola-Abitia P, Beattie WG, Beattie KL (1999) Mutation detection by stacking hybridization on genosensor arrays. Mol Biotechnol 11(1):13–25

    Article  PubMed  CAS  Google Scholar 

  18. American Thyroid Association Guidelines Task Force, Kloos RT, Eng C, Evans DB, Francis GL, Gagel RF, Gharib H, Moley JF, Pacini F, Ringel MD, Schlumberger M, Wells SA Jr (2009) Medullary thyroid cancer: management guidelines of the American thyroid association. Thyroid 19(6):565–612

    Google Scholar 

  19. Donis-Keller H (1995) The RET proto-oncogene and cancer. J Intern Med 238(4):319–325

    Article  PubMed  CAS  Google Scholar 

  20. Bednar M (2000) DNA microarray technology and application. Med Sci Monit 6(4):796–800

    PubMed  CAS  Google Scholar 

  21. Brown PO, Botstein D (1999) Exploring the new world of the genome with DNA microarrays. Nat Genet 21(1):33–37

    Article  PubMed  CAS  Google Scholar 

  22. Debouck C, Goodfellow PN (1999) DNA microarrays in drug discovery and development. Nat Genet 21(1):48–50

    Article  PubMed  CAS  Google Scholar 

  23. Kim IJ, Kang HC, Park JH, Ku JL, Lee JS, Kwon HJ, Yoon KA, Heo SC, Yang HY, Cho BY, Kim SY, Oh SK, Youn YK, Park DJ, Lee MS, Lee KW, Park JG (2002) RET oligonucleotide microarray for the detection of RET mutations in multiple endocrine neoplasia type 2 syndromes. Clin Cancer Res 8(2):457–463

    PubMed  CAS  Google Scholar 

  24. Zenaty D, Aigrain Y, Peuchmaur M, Philippe-Chomette P, Baumann C, Cornelis F, Hugot JP, Chevenne D, Barbu V, Guillausseau PJ, Schlumberger M, Carel JC, Travagli JP, Léger J (2009) Medullary thyroid carcinoma identified within the first year of life in children with hereditary multiple endocrine neoplasia type 2A (codon 634) and 2B. Eur J Endocrinol 160(5):807–813

    Article  PubMed  CAS  Google Scholar 

  25. Marini F, Falchetti A, Del Monte F, Carbonell Sala S, Tognarini I, Luzi E, Brandi ML (2006) Multiple endocrine neoplasia type 2. Orphanet J Rare Dis 1:45

    Article  PubMed  Google Scholar 

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Authors and Affiliations

  1. Laboratorio de Diagnóstico Molecular, ENCB IPN, México city, México

    R. A. Pacheco-Rivera

  2. Servicio de Genética, Instituto Nacional de Rehabilitación, México city, México

    E. Hernández-Zamora

  3. Departamento de Biología Molecular, Universidad de Guanajuato, Guanajuato city, México

    B. González-Yebra

  4. Life Sciences Division, Oak Ridge National Laboratory, Oak Ridge, TN, USA

    K. Beattie

  5. Laboratorio de Biotecnología y Bioinformática Molecular, ENCB IPN, México city, México

    R. Maldonado-Rodríguez & J. C. Santiago-Hernández

  6. Servico de Endocrinologia, Hospital de Oncologia, CMN SXXI IMSS, México city, México

    M. E. Medrano-Ortiz de Zárate

  7. Laboratorio de Oncología Genómica, UIMEO-CMN SXXI, IMSS, México city, México

    R. A. Pacheco-Rivera & M. Salcedo

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  1. R. A. Pacheco-Rivera
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  2. E. Hernández-Zamora
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  3. B. González-Yebra
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  4. K. Beattie
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  5. R. Maldonado-Rodríguez
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  6. J. C. Santiago-Hernández
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  7. M. E. Medrano-Ortiz de Zárate
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  8. M. Salcedo
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Correspondence to E. Hernández-Zamora.

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Pacheco-Rivera, R.A., Hernández-Zamora, E., González-Yebra, B. et al. Single oligoarray-based detection of specific M918T mutation in RET oncogene in multiple endocrine neoplasia type 2B. Clin Exp Med 11, 227–234 (2011). https://doi.org/10.1007/s10238-010-0128-z

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  • DOI: https://doi.org/10.1007/s10238-010-0128-z

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