Analysis of and somatic mutations in differentiated thyroid cancers.

Anaplastic lymphoma kinase (), isocitrate dehydrogenase 1 and 2 ( and ) and matrix metalloproteinase 8 () gene mutations have been frequently reported in human cancers; however, to the best of our knowledge, they have not been specifically examined in differentiated thyroid cancers (DTCs). Therefore, the present study aimed to determine the somatic mutational frequencies of these genes in DTCs. Mutational analysis of the (exons 23, 24 and 25), (exon 4), (exon 4), and (all exons 1-10) was performed in 126, 271, 271 and 50 DTCs, respectively. All the indicated exons were PCR-amplified and the PCR products were directly sequenced by Sanger sequencing. The present study identified a high frequency (86%; 43/50) of single nucleotide polymorphism (SNP) and also found some rare SNPs of this gene (S3C, T32I, L310P and K460T) in DTCs but no somatic mutation in , , and . Analyses of 414 DTCs from The Cancer Genome Atlas revealed rare (1%) and (0.24%) mutations and none in and . Conversely, analyses of 117 aggressive thyroid cancers [84, poorly differentiated thyroid cancer (PDTC); 33, anaplastic thyroid cancer (ATC)] from the Memorial Sloan Kettering Cancer Center cohort revealed mutations in 3% of ATCs and fusions in 3.6% of PDTCs. mutation was identified in 1.25% of PDTCs but not in ATC. mutation was identified in 3% of ATCs but not in PDTC. The present study demonstrated that these genes are less frequently mutated in DTCs, but common in ATCs and PDTCs. It suggests that these genes serve a role in a small portion of DTCs and a more important role in ATCs and PDTCs and may serve as potential therapeutic targets in these subsets.