Potent mitogenicity of the RET/PTC3 oncogene correlates with its prevalence in tall-cell variant of papillary thyroid carcinoma

Fulvio Basolo, Riccardo Giannini, Carmen Monaco, Rosa Marina Melillo, Francesca Carlomagno, Martina Pancrazi, Giuliana Salvatore, Gennaro Chiappetta, Furio Pacini, Rossella Elisei, Paolo Miccoli, Aldo Pinchera, Alfredo Fusco, Massimo Santoro

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Abstract

The tall-cell variant (TCV) of papillary thyroid carcinoma (PTC), characterized by tall cells bearing an oxyphilic cytoplasm, is more clinically aggressive than conventional PTC. RET tyrosine kinase rearrangements, which represent the most frequent genetic alteration in PTC, lead to the recombination of RET with heterologous genes to generate chimeric RET/PTC oncogenes. RET/PTC1 and RET/PTC3 are the most prevalent variants. We have found RET rearrangements in 35.8% of TCV (14 of 39 cases). Whereas the prevalences of RET/PTC1 and RET/PTC3 were almost equal in classic and follicular PTC, all of the TCV-positive cases expressed the RET/PTC3 rearrangement. These findings prompted us to compare RET/PTC3 and RET/PTC1 in an in vitro thyroid model system. We have expressed the two oncogenes in PC Cl 3 rat thyroid epithelial cells and found that RET/ PTC3 is endowed with a strikingly more potent mitogenic effect than RET/PTC1. Mechanistically, this difference correlated with an increased signaling activity of RET/PTC3. In conclusion, we postulate that the correlation between the RET/PTC rearrangement type and the aggressiveness of human PTC is related to the efficiency with which the oncogene subtype delivers mitogenic signals to thyroid cells.

Original languageEnglish
Pages (from-to)247-254
Number of pages8
JournalAmerican Journal of Pathology
Volume160
Issue number1
Publication statusPublished - 2002

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Oncogenes
Thyroid Gland
Follicular Adenocarcinoma
Papillary Thyroid cancer
Protein-Tyrosine Kinases
Genetic Recombination
Cytoplasm
Genes

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

Basolo, F., Giannini, R., Monaco, C., Melillo, R. M., Carlomagno, F., Pancrazi, M., ... Santoro, M. (2002). Potent mitogenicity of the RET/PTC3 oncogene correlates with its prevalence in tall-cell variant of papillary thyroid carcinoma. American Journal of Pathology, 160(1), 247-254.

Potent mitogenicity of the RET/PTC3 oncogene correlates with its prevalence in tall-cell variant of papillary thyroid carcinoma. / Basolo, Fulvio; Giannini, Riccardo; Monaco, Carmen; Melillo, Rosa Marina; Carlomagno, Francesca; Pancrazi, Martina; Salvatore, Giuliana; Chiappetta, Gennaro; Pacini, Furio; Elisei, Rossella; Miccoli, Paolo; Pinchera, Aldo; Fusco, Alfredo; Santoro, Massimo.

In: American Journal of Pathology, Vol. 160, No. 1, 2002, p. 247-254.

Research output: Contribution to journalArticle

Basolo, F, Giannini, R, Monaco, C, Melillo, RM, Carlomagno, F, Pancrazi, M, Salvatore, G, Chiappetta, G, Pacini, F, Elisei, R, Miccoli, P, Pinchera, A, Fusco, A & Santoro, M 2002, 'Potent mitogenicity of the RET/PTC3 oncogene correlates with its prevalence in tall-cell variant of papillary thyroid carcinoma', American Journal of Pathology, vol. 160, no. 1, pp. 247-254.
Basolo, Fulvio ; Giannini, Riccardo ; Monaco, Carmen ; Melillo, Rosa Marina ; Carlomagno, Francesca ; Pancrazi, Martina ; Salvatore, Giuliana ; Chiappetta, Gennaro ; Pacini, Furio ; Elisei, Rossella ; Miccoli, Paolo ; Pinchera, Aldo ; Fusco, Alfredo ; Santoro, Massimo. / Potent mitogenicity of the RET/PTC3 oncogene correlates with its prevalence in tall-cell variant of papillary thyroid carcinoma. In: American Journal of Pathology. 2002 ; Vol. 160, No. 1. pp. 247-254.
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abstract = "The tall-cell variant (TCV) of papillary thyroid carcinoma (PTC), characterized by tall cells bearing an oxyphilic cytoplasm, is more clinically aggressive than conventional PTC. RET tyrosine kinase rearrangements, which represent the most frequent genetic alteration in PTC, lead to the recombination of RET with heterologous genes to generate chimeric RET/PTC oncogenes. RET/PTC1 and RET/PTC3 are the most prevalent variants. We have found RET rearrangements in 35.8{\%} of TCV (14 of 39 cases). Whereas the prevalences of RET/PTC1 and RET/PTC3 were almost equal in classic and follicular PTC, all of the TCV-positive cases expressed the RET/PTC3 rearrangement. These findings prompted us to compare RET/PTC3 and RET/PTC1 in an in vitro thyroid model system. We have expressed the two oncogenes in PC Cl 3 rat thyroid epithelial cells and found that RET/ PTC3 is endowed with a strikingly more potent mitogenic effect than RET/PTC1. Mechanistically, this difference correlated with an increased signaling activity of RET/PTC3. In conclusion, we postulate that the correlation between the RET/PTC rearrangement type and the aggressiveness of human PTC is related to the efficiency with which the oncogene subtype delivers mitogenic signals to thyroid cells.",
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AU - Basolo, Fulvio

AU - Giannini, Riccardo

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AU - Melillo, Rosa Marina

AU - Carlomagno, Francesca

AU - Pancrazi, Martina

AU - Salvatore, Giuliana

AU - Chiappetta, Gennaro

AU - Pacini, Furio

AU - Elisei, Rossella

AU - Miccoli, Paolo

AU - Pinchera, Aldo

AU - Fusco, Alfredo

AU - Santoro, Massimo

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AB - The tall-cell variant (TCV) of papillary thyroid carcinoma (PTC), characterized by tall cells bearing an oxyphilic cytoplasm, is more clinically aggressive than conventional PTC. RET tyrosine kinase rearrangements, which represent the most frequent genetic alteration in PTC, lead to the recombination of RET with heterologous genes to generate chimeric RET/PTC oncogenes. RET/PTC1 and RET/PTC3 are the most prevalent variants. We have found RET rearrangements in 35.8% of TCV (14 of 39 cases). Whereas the prevalences of RET/PTC1 and RET/PTC3 were almost equal in classic and follicular PTC, all of the TCV-positive cases expressed the RET/PTC3 rearrangement. These findings prompted us to compare RET/PTC3 and RET/PTC1 in an in vitro thyroid model system. We have expressed the two oncogenes in PC Cl 3 rat thyroid epithelial cells and found that RET/ PTC3 is endowed with a strikingly more potent mitogenic effect than RET/PTC1. Mechanistically, this difference correlated with an increased signaling activity of RET/PTC3. In conclusion, we postulate that the correlation between the RET/PTC rearrangement type and the aggressiveness of human PTC is related to the efficiency with which the oncogene subtype delivers mitogenic signals to thyroid cells.

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