Abstract 1755P
Background
Anaplastic thyroid carcinomas (ATCs) are fast-growing carcinomas, with a dismal prognosis. Several studies have attempted to identify new biomarkers involved in its development and behavior. The role played by EIF1AX mutations has not been fully clarified. There are significant discrepancies related to their overall frequency and mutation location.
Methods
By genotyping 69 tumor areas from 36 patients we sought to determine the prevalence, clonal nature, and implication in tumor progression of EIF1AX mutations. Mutational analysis was performed by PCR and SSCP or direct sequencing. Mutations at TERTp, BRAF, NRAS, KRAS, HRAS, and PIK3CA were evaluated in parallel to assess the level of concurrence and degree of intratumoral heterogeneity (ITGH).
Results
EIF1AX mutations were found in 8 cases(22.2%). The c.338-1G>T mutation, previously associated with thyroid cancer, did not show. Half of the mutated cases resulted clonal. EIF1AX was mutated in 50% of the cases in which a better differentiated area was investigated (8/16) and in half of those cases, it was involved in progression. In 6 cases (75%) EIF1AX mutations coexisted with other mutational events [RAS+EIF1AX (50%), BRAF+EIF1AX (33%), PIK3CA+EIF1AX (50%),TERTp+EIF1AX (100%)]. In 28 cases at least one of the 7 genes analysed resulted mutated (77.8%) [TERTp(61%), BRAF (33.3%), KRAS (8.3%), NRAS(17%), PIK3CA(22.9%) and EIF1AX(22.2%)]. ITGH was seen in 20 cases (55.6%).
Conclusions
The prevalence of EIF1AX mutations is within the range previously reported in ATC [9-33%] and much higher than in better differentiated thyroid carcinomas. EIF1AX does not seem to have a hotspot mutation as other works have reported. In agreement with the high degree of genomic instability in ATCs, EIF1AX mutations appear frequently associated with mutations in other genes. Oncogenic EIF1AX activation should be taken into consideration when applying targeted therapies to ATC patients.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
University of Valladolid- IBGM.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.