High Prevalence of 5'UTR Mutations in Anaplastic Thyroid Cancer.

Anaplastic thyroid cancer (ATC) is a rare but one of the most lethal types of human cancer. Although increasing evidence demonstrated that ATC tumors had a high mutation burden, little is known about the aberrancy of the noncoding genome of ATC except the well-investigated () promoter mutations. The mutational statuses of 5' untranslated region (5'UTR), intron 6, and promoters, as well as the promoter and mutations were determined using Sanger sequencing in 28 patients with ATC (19 women and 9 men) with a median (interquartile range) age of 64 (55-71) years, 14 thyroid cancer cell lines and a normal thyroid cell line. The prevalence of 5'UTR mutations in papillary thyroid cancer (PTC) and their association with clinicopathologic characteristics were explored by analyzing The Cancer Genome Atlas thyroid cancer dataset. The noncoding mutations in , and promoters, 5'UTR, and intron 6 were collectively found in 82.1% (23/28) of ATC samples. Specifically, promoter mutations were detected in 22 (78.6%) samples; intron mutations were detected in 2 (7.1%) samples; and both and promoter mutations were detected in 1 (3.6%) ATC sample. Two hotspot mutations in 5'UTR were observed in 14 of 28 (50%) ATCs, 7 of 492 (1.4%) PTCs, and 1 cell line derived from ATC. 5'UTR mutations were significantly associated with older age at diagnosis (60 vs. 46 for wild type, = 0.003), pathological T3/T4 stage (85.7% vs. 37.7%, = 0.010), and advanced tumor stages (85.7% vs. 32.5%, = 0.006) in PTC. This preliminary study for the first time showed a high prevalence of 5'UTR mutations in ATC and indicated an association between mutation and aggressive characteristics of PTC, which needs to be confirmed in large cohort studies.