Pathogenesis of adult radiation-associated papillary thyroid carcinoma. Characteristics at its early step

The major histotype of thyroid cancer induced by radiation is the papillary thyroid carcinoma (PTC). This paper describes comparisons of prevalence of sporadic and radiation-associated PTC, and of their observed gene mutations to consider PTC pathogenesis. In 70% or more of PTC, genes associated with mitogen-activated protein kinase (MAPK) signaling pathway are known to be altered and the mutations are mostly rearrangements (Rea) of RET/PTC, NTRK and BRAF, and point mutations (Pom) of RAS and BRAF. One of these mutations, once occurred, can be conceivably the important initiation of PTC pathogenesis and the signaling is continuously activated to result in abnormal control of cell cycle and gene instability. RET/PTC Rea and BRAF Pom play the major role in the activation of MAPK signaling pathway. In 52 cases of adult A-bomb survivors' PTC, most frequently detected is RET/PTC Rea (11 cases) relative to 21 non-exposed people's PTC (only 1 case). The relative frequency (ref) of survivors' PTC with the Rea, Pom and other unknown mutation (Um) is found significantly increased, decreased and tended to increase, respectively, along with the exposed dose. As for the time after exposure to PTC crisis, ref of PTC with Pom and Um is found to increase and tending to decrease, respectively, with the time, and ref of PTC with Rea, to have a peak at the time interval 21-30 years. Ref of PTC with Pom increases with age at the exposure and median of the exposure age is significantly younger in PTC with Rea than Pom. As above, RET/PTC Rea in thyroid epithelium can be a major pathogenesis of radiation-induced PTC. (K.T)