Classical point mutations of RET, BRAF and RAS oncogenes are not shared in papillary and medullary thyroid cancer occurring simultaneously in the same gland

• Published in: Journal of endocrinological investigation Vol. 40; no. 1; pp. 55 - 62
• Main Authors: Ciampi, R., Romei, C., Pieruzzi, L., Tacito, A., Molinaro, E., Agate, L., Bottici, V., Casella, F., Ugolini, C., Materazzi, G., Basolo, F., Elisei, R.
• Format: Journal Article
• Language: English
• Published: Cham Springer International Publishing 2017; Springer Nature B.V
• Subjects: Adult; Aged; Aged, 80 and over; Biomarkers, Tumor - genetics; Carcinoma, Medullary - genetics; Carcinoma, Papillary - genetics; Endocrinology; Female; Humans; Male; Medicine; Medicine & Public Health; Metabolic Diseases; Middle Aged; Oncogenes; Original Article; Point Mutation - genetics; Polymerase Chain Reaction; Proto-Oncogene Proteins B-raf - genetics; Proto-Oncogene Proteins c-ret - genetics; ras Proteins - genetics; Thyroid Neoplasms - genetics; Tumor Cells, Cultured; Simultaneous tumors; Molecular biology; Medullary thyroid carcinoma; Papillary thyroid carcinoma
• ISSN: 1720-8386; 0391-4097; 1720-8386
• DOI: 10.1007/s40618-016-0526-5

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.