Background: Papillary (PTC) and medullary (MTC) thyroid carcinomas represent two distinct entities, but quite frequently, they may occur simultaneously.
Aim: To provide genetic analysis of PTC and MTC occurring in the same patient (PTC/MTC) to elucidate their origin.
Methods: Sequencing analysis of RAS, BRAF and RET oncogenes hot spots mutations in tumoral and normal tissues of 24 PTC/MTC patients.
Results: Two of 24 patients (8.3 %) were affected by familial MTC (FMTC) harboring RET germline mutations in all tissues. Eight of 22 (36.4 %) sporadic cases did not show any somatic mutation in the three tissue components. Considering the MTC component, 10/22 (45.4 %) patients did not show any somatic mutation, 7 of 22 (31.8 %) harbored the M918T RET somatic mutation and 4/22 (18.2 %) presented mutations in the H-RAS gene. In an additional case (1/22, 4.6 %), H-RAS and RET mutations were simultaneously present. Considering the PTC component, 1 of 24 (4.2 %) patients harbored the V600E BRAF mutation, 1 of 24 (4.2 %) the T58A H-RAS mutation and 1 of 24 (4.2 %) the M1T K-RAS mutation, while the remaining PTC cases did not show any somatic mutation. In one case, the MTC harbored a RET mutation and the PTC a BRAF mutation. None of the mutations found were present in both tumors.
Conclusions: To our knowledge, this is the first study analyzing a possible involvement of RET, BRAF and RAS oncogene mutations in PTC/MTC. These data clearly suggest that the classical activating mutations of the oncogenes commonly involved in the pathogenesis of PTC and MTC may not be responsible for their simultaneous occurrence.
Keywords: Medullary thyroid carcinoma; Molecular biology; Papillary thyroid carcinoma; Simultaneous tumors.