Surgery
Volume 146, Issue 6 , Pages 998-1005 , December 2009

One hundred and seven family members with the rearranged during transfection V804M proto-oncogene mutation presenting with simultaneous medullary and papillary thyroid carcinomas, rare primary hyperparathyroidism, and no pheochromocytomas: Is this a new syndrome—MEN 2C?

  • Alexander L. Shifrin, MD, FACS

      Affiliations

    • Department of Surgery, Jersey Shore University Medical Center, Neptune, NJ
    • Corresponding Author InformationReprint requests: Alexander L. Shifrin, MD, FACS, Jersey Shore University Medical Center, Department of Surgery, 1945 State Route 33, Neptune, NJ 07754.
    • ,
  • Cristina Xenachis, MD

      Affiliations

    • Downtown Osteoporosis Center, Matawan, NJ
    • ,
  • Angela Fay, MS, CGC

      Affiliations

    • Department of Oncology, Jersey Shore University Medical Center, Neptune, NJ
    • ,
  • Theodore J. Matulewicz, MD

      Affiliations

    • Department of Pathology, Jersey Shore University Medical Center, Neptune, NJ
    • ,
  • Yen-Hong Kuo, ScM, MS

      Affiliations

    • Department of Academic Affairs, Jersey Shore University Medical Center, Neptune, NJ
    • ,
  • Jerome J. Vernick, MD, FACS

      Affiliations

    • Department of Surgery, Jersey Shore University Medical Center, Neptune, NJ

,Accepted 24 September 2009.

References 

  1. Castellone MD, Santoro M. Dysregulated RET signaling in thyroid cancer. Endocrinol Metab Clin North Am. 2008;37:363–374
  2. Takahashi M, Ritz J, Cooper GM. Activation of a novel human transforming gene, ret, by DNA rearrangement. Cell. 1985;42:581–588
  3. Donis-Keller H, Dou S, Chi D, Carlson KM, Toshima K, Lairmore TC, et al. Mutations in the RET proto-oncogene are associated with MEN 2A and FMTC. Hum Mol Genet. 1993;2:851–856
  4. Mulligan LM, Kwok JB, Healey CS, Elsdon MJ, Eng C, Gardner E, et al. Germ-line mutations of the RET proto-oncogene in multiple endocrine neoplasia type 2A. Nature. 1993;363:458–460
  5. Eng C, Smith DP, Mulligan LM, Nagai MA, Healey CS, Ponder MA, et al. Point mutation within the tyrosine kinase domain of the RET proto-oncogene in multiple endocrine neoplasia type 2B and related sporadic tumours. Hum Mol Genet. 1994;3:237–241
  6. Carlson KM, Dou S, Chi D, Scavarda N, Toshima K, Jackson CE, et al. Single missense mutation in the tyrosine kinase catalytic domain of the RET protooncogene is associated with multiple endocrine neoplasia type 2B. Proc Natl Acad Sci U S A. 1994;91:1579–1583
  7. Eng C, Clayton D, Schuffenecker I, Lenoir G, Cote G, Gagel RF, et al. The relationship between specific RET proto-oncogene mutations and disease phenotype in multiple endocrine neoplasia type 2. International RET mutation consortium analysis. JAMA. 1996;276:1575–1579
  8. Brandi ML, Gagel RF, Angeli A, Bilezikian JP, Beck-Peccoz P, Bordi C, et al. Guidelines for diagnosis and therapy of MEN type 1 and type 2. J Clin Endocrinol Metab. 2001;86:5658–5671
  9. Fink M, Weinhüsel A, Niederle B, Haas OA. Distinction between sporadic and hereditary medullary thyroid carcinoma (MTC) by mutation analysis of the RET proto-oncogene. “Study Group Multiple Endocrine Neoplasia Austria (SMENA).”. Int J Cancer. 1996;69:312–316
  10. Learoyd DL, Gosnell J, Elston MS, Saurine TJ, Richardson AL, Delbridge LW, et al. Experience of prophylactic thyroidectomy in multiple endocrine neoplasia type 2A kindreds with RET codon 804 mutations. Clin Endocrinol (Oxf). 2005;63:636–641
  11. Gibelin H, Bezieau S, Misso C, Bouin-Pineau MH, Maréchaud R, Kraimps JL. Germline RET V804M mutation associated with multiple endocrine neoplasia type 2A. Br J Surg. 2004;91:1458–1459
  12. Pinna G, Orgiana G, Riola A, Ghiani M, Lai ML, Carcassi C, et al. RET proto-oncogene in Sardinia: V804M is the most frequent mutation and may be associated with FMTC/MEN-2A phenotype. Thyroid. 2007;17:101–104
  13. Feldman GL, Edmonds MW, Ainsworth PJ, Schuffenecker I, Lenoir GM, Saxe AW, et al. Variable expressivity of familial medullary thyroid carcinoma (FMTC) due to a RET V804M (GTG–>ATG) mutation. Surgery. 2000;128:93–98
  14. Frohnauer MK, Decker RA. Update on the MEN 2A c804 RET mutation: is prophylactic thyroidectomy indicated?. Surgery. 2000;128:1052–1057
  15. Decker R, Peacock M. Update on the profile of multiple endocrine neoplasia type 2a RET mutations. Cancer Supplements. 1997;80:557–568
  16. Fattoruso O, Quadro L, Libroia A, Verga U, Lupoli G, Cascone E, et al. A GTG to ATG novel point mutation at codon 804 in exon 14 of the RET proto-oncogene in two families affected by familial medullary thyroid carcinoma. Hum Mutat. 1998;Suppl 1:S167–S171
  17. Brauckhoff M, Gimm O, Hinze R, Ukkat J, Brauckhoff K, Dralle H. Papillary thyroid carcinoma in patients with RET proto-oncogene germline mutation. Thyroid. 2002;12:557–561
  18. Dionigi G, Castano P, Bertolini V, Boni L, Rovera F, Tanda ML, et al. Simultaneous medullary and papillary thyroid cancer: two case reports. J Med Case Reports. 2007;1:133
  19. Papi G, Corrado S, Pomponi MG, Carapezzi C, Cesinaro A, LiVolsi VA. Concurrent lymph node metastases of medullary and papillary thyroid carcinoma in a case with RET oncogene germline mutation. Endocr Pathol. 2003;14:269–276
  20. Foppiani L, Forzano F, Ceccherini I, Bruno W, Ghiorzo P, Caroli F, et al. Uncommon association of germline mutations of RET proto-oncogene and CDKN2A gene. Eur J Endocrinol. 2008;158:417–422
  21. Shaha AR, Cohen T, Ghossein R, Tuttle RM. Late-onset medullary carcinoma of the thyroid: need for genetic testing and prophylactic thyroidectomy in adult family members. Laryngoscope. 2006;116:1704–1707
  22. Lecube A, Hernandez C, Oriola J, Galard R, Gémar E, Mesa J, et al. V804 M RET mutation and familial medullary thyroid carcinoma: report of a large family with expression of the disease only in the homozygous gene carriers. Surgery. 2002;131:509–514
  23. Miccoli P, Minuto MN, Galleri D, D'Agostino J, Basolo F, Antonangeli L, et al. Incidental thyroid carcinoma in a large series of consecutive patients operated on for benign thyroid disease. Aust N Z J Surg. 2006;76:123–126
  24. Recasens M, Oriola J, Fernández-Real JM, Roig J, Rodríguez-Hermosa JI, Font JA, et al. Asymptomatic bilateral adrenal pheochromocytoma in a patient with a germline V804M mutation in the RET proto-oncogene. Clin Endocrinol (Oxf). 2007;67:29–33
  25. Sippel RS, Kunnimalaiyaan M, Chen H. Current management of medullary thyroid cancer. Oncologist. 2008;13:539–547

PII: S0039-6060(09)00562-5

doi: 10.1016/j.surg.2009.09.021

Surgery
Volume 146, Issue 6 , Pages 998-1005 , December 2009

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