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Analysis of RET proto-oncogene abnormalities in patients with MEN 2A, MEN 2B, familial or sporadic medullary thyroid carcinoma

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Abstract

Medullary thyroid carcinoma (MTC) may occur either as a sporadic or familial (FMTC) disease. Multiple endocrine neoplasia (MEN) type 2, inherited as an autosomal dominant disease, is characterized by coexistence of MTC with other endocrine neoplasia. Activating mutations of the RET proto-oncogene, involving the somatic or the germinal cell lineage, are found in both inherited and acquired forms. In this study, RET mutations were screened in 47 individuals either affected by MTC or belonging to families with hereditary MTC. Exons 10, 11, 13, 14, 15 and 16 of the RET gene were amplified by polymerase chain reaction and examined by DNA sequence and/or restriction enzyme analysis to detect mutations in purified amplicons. Six MEN 2A families with a germline mutation at codon 634, one FMTC family carrying a mutation at codon 618 and two MEN 2B families with a mutation at codon 918 were identified. In affected members of a MEN 2A family no known RET mutations were observed. Besides, we identified a germline mutation in a patient with apparently sporadic MTC and in two out of three sons, indicating the presence of a sporadic misclassified familial disease. In all of the families examined we were able to distinguish the affected vs unaffected (not at risk) members. A somatic mutation of codon 918 was detected in three out of ten patients with apparently sporadic MTC.

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Authors and Affiliations

  1. Cattedra di Endocrinologia, Dipartimento di Medicina Sperimentale e Clinica, Via T. Campanella, 88100, Catanzaro, Italy

    E. Chiefari, F. Arturi & Sebastiano Filetti M.D.

  2. Cattedra di Farmacologia, Facoltà di Farmacia, Università di Catanzaro, Catanzaro, Italy

    D. Russo

  3. Istituto di Medicina Interna e di Malattie Endocrine e del Metabolismo, Cattedra di Endocrinologia, Università di Catania, Catania, Italy

    D. Giuffrida

  4. Divisione di Endocrinologia, Ospedale Maggiore, Bologna, Italy

    G. A. Zampa

  5. Unità Operativa di Endocrinologia, Ospedale Bentivoglio Bologna, Bologna, Italy

    D. Meringolo & D. Bianchi

  6. Istituto di Ricovero e Cura a Carattere Scientifico, Casa Sollievo della Sofferenza, S.G. Rotondo, Foggia, Italy

    I. Chiodini & V. Trischitta

  7. Cattedra di Endocrinologia, Ospedale “V. Cervello”, Palermo, Italy

    M. Attard

  8. Ospedale Civile di Tinchi, Matera, Italy

    R. Bruno & P. Giannasio

  9. Cattedra di Endocrinologia, Università Cattolica, Laboratorio di Oncogenesi Molecolare, Istituto Tumori Regina Elena, Roma, Italy

    A. Pontecorvi

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  1. E. Chiefari
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  2. D. Russo
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  3. D. Giuffrida
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  4. G. A. Zampa
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  5. D. Meringolo
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  6. F. Arturi
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  7. I. Chiodini
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  8. D. Bianchi
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  9. M. Attard
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  10. V. Trischitta
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  11. R. Bruno
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  13. A. Pontecorvi
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  14. Sebastiano Filetti M.D.
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Chiefari, E., Russo, D., Giuffrida, D. et al. Analysis of RET proto-oncogene abnormalities in patients with MEN 2A, MEN 2B, familial or sporadic medullary thyroid carcinoma. J Endocrinol Invest 21, 358–364 (1998). https://doi.org/10.1007/BF03350771

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  • DOI: https://doi.org/10.1007/BF03350771

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