Research Papers:

RET mutation heterogeneity in primary advanced medullary thyroid cancers and their metastases

Cristina Romei _, Raffaele Ciampi, Francesca Casella, Alessia Tacito, Liborio Torregrossa, Clara Ugolini, Fulvio Basolo, Gabriele Materazzi, Paolo Vitti and Rossella Elisei

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Oncotarget. 2018; 9:9875-9884. https://doi.org/10.18632/oncotarget.23986

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Cristina Romei1, Raffaele Ciampi1, Francesca Casella1, Alessia Tacito1, Liborio Torregrossa2, Clara Ugolini2, Fulvio Basolo2, Gabriele Materazzi2, Paolo Vitti1 and Rossella Elisei1

1Endocrine Unit, Department of Clinical and Experimental Medicine, University Hospital of Pisa, Pisa, Italy

2Department of Surgical, Medical and Molecular Pathology, University Hospital of Pisa, Pisa, Italy

Correspondence to:

Rossella Elisei, email: [email protected]

Keywords: medullary thyroid carcinoma; RET; genetic instability; tumor clonality

Received: August 09, 2017     Accepted: November 16, 2017     Published: January 04, 2018


Purpose: Medullary Thyroid Cancer (MTC) whose pathogenesis is strictly related to RET proto-oncogene alterations, has been shown to have a heterogenic RET mutation profile in subpopulations of MTC. The aim of our study was to investigate the RET somatic mutation profile in primary MTC and in the corresponding metastatic tissues in a series of advanced metastatic cases.

Results: This study demonstrated that in about 20% of cases a different RET mutation profile can be found when comparing primary tumor and its corresponding metastases. Furthermore in 8% of tumors, RETintratumor heterogeneity was observed We also showed that in some cases an imbalance of RET copy number was present. We confirmed a high prevalence (90%) of RET somatic mutations in advanced tumors.

Materials and Methods: Fifty-six MTC patients (50 somatic and 6 hereditary cases) have been included in the study and a total of 209 specimens have been analysed by direct sequencing. Multiplex ligation-dependent probe amplification (MLPA) has been used to investigate amplification/deletion of RET alleles.

Conclusions: In conclusion, this study showed a genetic intra- and intertumor heterogeneity in MTC, But in only 20% of CASES These results could justify the relatively moderate level of aggressiveness of the disease with respect to more aggressive human tumors that are characterized by a high rate of mutation and heterogeneity.

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