This is the first reported case of an acquired KRAS-activating mutation that developed during treatment with BRAF and MEK inhibition in a patient with BRAF-mutated PTC.
We found rs11246050 in NLRP6 (dominant model, OR/95% CI: 2.028/1.091-3.769, p = 0.025), rs2286742 and rs3740530 in HABP2 (recessive model, OR/95% CI: 9.644/1.307-71.16, p = 0.026 and 3.989/1.413-11.26, p = 0.009), rs2736098 in TERT (recessive model, OR/95% CI: 2.322/1.028-5.242. p = 0.042) and rs62054619 in GAS8-AS1 (recessive model, OR/95% CI: 2.219/1.067-4.617, p = 0.033) were associated with the risk of PTC. rs1137282 in KRAS (dominant model, OR/95% CI: 0.5430/0.3192-0.9236, p = 0.024), rs1347591 and rs4461062 in NUP93 (dominant model, OR/95% CI: 0.6121/0.4128-0.9076, p = 0.015 and 0.6156/0.4157-0.9117, p = 0.015) were associated with low risk of distant metastatic disease in PTC patients. rs33954691 in TERT was associated with the risk of RR-PTC under dominant model (OR/95% CI: 3.161/1.596-6.262).
Thyroid nodules with KRAS mutations are different from nodules with NRAS and HRAS mutations with regard to cytopathologic and histopathologic outcome characteristics.
Twenty-five PTCs (11 with BRAF(V600E), 4 with RET/PTC1, and 10 without mutation in HRAS, KRAS, NRAS, BRAF, RET/PTC1, or RET/PTC3) were analyzed using Genome-Wide Human SNP Array 6.0 which allows us to detect copy number alteration (CNA) and uniparental disomy (UPD), also referred to as copy neutral loss of heterozygosity, in a single experiment.
A KRAS codon 12 mutation, the GGT → GTT transversion, corresponding to the Gly → Val amino acid change was identified in the absence of other genetic alterations commonly found in PTC.
Finally, KRAS2 was found to be differentially expressed (P<0.05) when comparing the papillary thyroid carcinoma and follicular thyroid carcinoma groups.