; 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
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.
MLPA was then used to study amplification/deletion of the RET gene.
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.