Papillary (PTC) and Medullary (MTC) thyroid carcinomas have distinct embryonic origins although they share the activation of common oncogenes (RET, RAS). The occurrence of these tumors in the same gland is not a rare event. Aim of this study was to investigate the hypothetical involvement of common genetic alterations in the symultaneous occurrence of the PTC and MTC. We studied 24 patients presenting simultaneous PTC and MTC. DNA was obtained from both tumor components and healthy tissue and sequenced for mutations in codons 12, 13 and 61 of H-, K- and N-RAS, 600 of BRAF and 634 and 918 of RET. Two/24 patients (8.3 %) were affected by MEN2A and carrying germline mutations of the RET gene (S981A, V804M). None of the patients showed mutations in the healthy tissue and 8/24 patients (33.4 %) had no mutations either in the tumor components. In the other cases, considering the MTC component: 8/24 (33.3 %) harboured the RET/M918T mutation; 3/24 (12.5 %) mutations in the H-RAS gene (G13R, Q61R, D69N) and 1/24 (4.2 %) showed simultaneously the H-RAS/Q61K and the RET/M918T mutations. In the PTC component: 1/24 (4.2 %) harboured the BRAF/V600E mutation, 1/24 (4.2 %) the H-RAS/T58A mutation and 1/24 (4.2 %) the K-RAS/M1T mutation. In one case, we found the RET (M918T) mutation in the MTC component and the BRAF/V600E in the PTC component. None of the mutations found were present in both tumors. These data suggest independent genetic causes in the development of simultaneous PTC and MTC. Confirmation of this hypothesis is that one of the patients showed simultaneous mutation of RET in MTC and the BRAF mutation in PTC. In this study we also found novel H-RAS and K-RAS mutations suggesting that alterations outside the classic hot spots may play a role in the pathogenesis of these tumors.
SIMULTANEOUS MEDULLARY AND PAPILLARY THYROID CARCINOMAS SHOW INDEPENDENT GENETIC ORIGIN
CIAMPI, RAFFAELE;ROMEI, CRISTINA;TACITO, ALESSIA;Ugolini, Clara;BASOLO, FULVIO;MATERAZZI, GABRIELE;ELISEI, ROSSELLA
2014-01-01
Abstract
Papillary (PTC) and Medullary (MTC) thyroid carcinomas have distinct embryonic origins although they share the activation of common oncogenes (RET, RAS). The occurrence of these tumors in the same gland is not a rare event. Aim of this study was to investigate the hypothetical involvement of common genetic alterations in the symultaneous occurrence of the PTC and MTC. We studied 24 patients presenting simultaneous PTC and MTC. DNA was obtained from both tumor components and healthy tissue and sequenced for mutations in codons 12, 13 and 61 of H-, K- and N-RAS, 600 of BRAF and 634 and 918 of RET. Two/24 patients (8.3 %) were affected by MEN2A and carrying germline mutations of the RET gene (S981A, V804M). None of the patients showed mutations in the healthy tissue and 8/24 patients (33.4 %) had no mutations either in the tumor components. In the other cases, considering the MTC component: 8/24 (33.3 %) harboured the RET/M918T mutation; 3/24 (12.5 %) mutations in the H-RAS gene (G13R, Q61R, D69N) and 1/24 (4.2 %) showed simultaneously the H-RAS/Q61K and the RET/M918T mutations. In the PTC component: 1/24 (4.2 %) harboured the BRAF/V600E mutation, 1/24 (4.2 %) the H-RAS/T58A mutation and 1/24 (4.2 %) the K-RAS/M1T mutation. In one case, we found the RET (M918T) mutation in the MTC component and the BRAF/V600E in the PTC component. None of the mutations found were present in both tumors. These data suggest independent genetic causes in the development of simultaneous PTC and MTC. Confirmation of this hypothesis is that one of the patients showed simultaneous mutation of RET in MTC and the BRAF mutation in PTC. In this study we also found novel H-RAS and K-RAS mutations suggesting that alterations outside the classic hot spots may play a role in the pathogenesis of these tumors.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
