Romei, Cristina1; Casella, Francesca1; Tacito, Alessia1: Ciampi, Raffaele1; Molinaro, Eleonora1; Agate, Laura1; Bottici, Valeria1; Matrone, Antonio1; Elisei, Rossella1
1 Unit of Endocrinology, Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy
Background: In this study, aimed to investigate genetic heterogeneity in MTC, we analyzed RET mutation profile in primary tumors and in corresponding metastases of 49 sporadic patients.
Methods: MLPA was then used to study amplification/deletion of the RET gene.
Results: Forty-four/49 (89.7%) patients showed the presence of a RET somatic mutation. In 39/49 cases 79.5%) a corresponding mutation profile was found in different types of tissue. In 10 cases (20.5%) a different RET mutation profile was observed in the primary tumor and in the metastases. Among these, 6 patients had a somatic RET alteration in the primary tumor but not in 6/35 (17%) metastases. In 2 cases a second RET mutation was found in the metastasis. A complex genetic heterogeneity was demonstrated in one MTC patient with a severe disease. The primary tumor and 5/7 metastases displayed a heterozygous 6 bp in frame deletion in exon 11. In a liver metastasis the deletion was homozygous. In this patient, MLPA analysis demonstrated a RET amplification in the primary tumor and a RET deletion in the liver metastasis.
Conclusion & Conclusion: In conclusion, our study shows that a) the prevalence of RET somatic alterations is elevated in metastatic MTC; b) about 22% of cases have a different RET mutation profile in the primary tumor and in the metastases; c) amplification/deletion of the RET gene can occur.
This information should be taken into consideration in the planning of personalized target therapies and raise the question of whether RET mutations play a real driving role in the development of MTC.