A new germline point mutation in Ret exon 8 (Cys515Ser) in a family with medullary thyroid carcinoma

Francesca Fazioli, Gina Piccinini, Gloria Appolloni, Roberta Bacchiocchi, Gioia Palmonella, Rina Recchioni, Elisa Pierpaoli, Francesca Silvetti, Marina Scarpelli, Matteo Bruglia, Rosa Marina Melillo, Massimo Santoro, Marco Boscaro, Augusto Taccaliti

Research output: Contribution to journalArticle

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Abstract

Background: A novel Cys-Ser Ret germline point mutation in a 58-year-old woman with bilateral medullary thyroid carcinoma (MTC) prompted us to perform genetic analysis of the family and evaluate the biological consequences of such a mutation. Methods: Ret analysis by direct sequencing was performed in five family members. The biological activity and biochemical properties of the Ret- Cys515Ser mutant were analyzed in NIH-3T3 cells. Results: The proband's son, age 35, had the Ret- Cys515Ser mutation and the L769 CTT/CTG exon 13 polymorphic variant, which was also found in his father. Clinical evaluation of the son also revealed bilateral multifocal microscopic MTC and papillary thyroid carcinoma (PTC). In vitro and in vivo analysis indicated ligand-independent activation of the Ret-Cys515Ser mutant due to aberrant disulfide homodimerization, increased mitogenic activity, and ability to induce anchorage-independent growth in NIH-3T3 cells in comparison to wild-type Ret, suggesting a possible role of Cys515Ser in tumor development. Conclusions: The Cys515Ser mutation adds to cysteine substitution groups that have been described in association with MTC. Our data also highlight the importance of performing a complete genetic analysis in patients who present with MTC.

Original languageEnglish
Pages (from-to)775-782
Number of pages8
JournalThyroid
Volume18
Issue number7
DOIs
Publication statusPublished - Jul 1 2008

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Germ-Line Mutation
Point Mutation
Exons
NIH 3T3 Cells
Nuclear Family
Mutation
Aptitude
Fathers
Disulfides
Cysteine
Ligands
Medullary Thyroid cancer
Growth
Neoplasms

ASJC Scopus subject areas

  • Endocrinology

Cite this

Fazioli, F., Piccinini, G., Appolloni, G., Bacchiocchi, R., Palmonella, G., Recchioni, R., ... Taccaliti, A. (2008). A new germline point mutation in Ret exon 8 (Cys515Ser) in a family with medullary thyroid carcinoma. Thyroid, 18(7), 775-782. https://doi.org/10.1089/thy.2007.0365

A new germline point mutation in Ret exon 8 (Cys515Ser) in a family with medullary thyroid carcinoma. / Fazioli, Francesca; Piccinini, Gina; Appolloni, Gloria; Bacchiocchi, Roberta; Palmonella, Gioia; Recchioni, Rina; Pierpaoli, Elisa; Silvetti, Francesca; Scarpelli, Marina; Bruglia, Matteo; Melillo, Rosa Marina; Santoro, Massimo; Boscaro, Marco; Taccaliti, Augusto.

In: Thyroid, Vol. 18, No. 7, 01.07.2008, p. 775-782.

Research output: Contribution to journalArticle

Fazioli, F, Piccinini, G, Appolloni, G, Bacchiocchi, R, Palmonella, G, Recchioni, R, Pierpaoli, E, Silvetti, F, Scarpelli, M, Bruglia, M, Melillo, RM, Santoro, M, Boscaro, M & Taccaliti, A 2008, 'A new germline point mutation in Ret exon 8 (Cys515Ser) in a family with medullary thyroid carcinoma', Thyroid, vol. 18, no. 7, pp. 775-782. https://doi.org/10.1089/thy.2007.0365
Fazioli, Francesca ; Piccinini, Gina ; Appolloni, Gloria ; Bacchiocchi, Roberta ; Palmonella, Gioia ; Recchioni, Rina ; Pierpaoli, Elisa ; Silvetti, Francesca ; Scarpelli, Marina ; Bruglia, Matteo ; Melillo, Rosa Marina ; Santoro, Massimo ; Boscaro, Marco ; Taccaliti, Augusto. / A new germline point mutation in Ret exon 8 (Cys515Ser) in a family with medullary thyroid carcinoma. In: Thyroid. 2008 ; Vol. 18, No. 7. pp. 775-782.
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AU - Palmonella, Gioia

AU - Recchioni, Rina

AU - Pierpaoli, Elisa

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