期刊
MOLECULAR AND CLINICAL ONCOLOGY
卷 15, 期 4, 页码 -出版社
SPANDIDOS PUBL LTD
DOI: 10.3892/mco.2021.2373
关键词
anaplastic lymphoma kinase; isocitrate dehydrogenase 1; isocitrate dehydrogenase 2; matrix metalloproteinase 8; mutation; cancer; oncogene; thyroid; tumor suppressor; differentiated thyroid cancer
类别
资金
- King Abdulaziz City for Science and Technology (KACST), Riyadh, Saudi Arabia [12-BIO2952-20]
The study revealed that ALK, IDH1, IDH2, and MMP8 gene mutations are less frequent in differentiated thyroid cancers (DTCs), but more common in aggressive thyroid cancers such as poorly differentiated thyroid cancer (PDTC) and anaplastic thyroid cancer (ATC). These genes may serve as potential therapeutic targets in ATCs and PDTCs, highlighting their importance in these subsets of thyroid cancers.
Anaplastic lymphoma kinase (ALK), isocitrate dehydrogenase 1 and 2 (IDH1 and IDH2) and matrix metalloproteinase 8 (MMP8) 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 ALK (exons 23, 24 and 25), IDH1 (exon 4), IDH2 (exon 4), and MMP8 (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 MMP8 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 ALK, IDH1, IDH2 and MMP8. Analyses of 414 DTCs from The Cancer Genome Atlas revealed rare ALK (1%) and MMP8 (0.24%) mutations and none in IDH1 and IDH2. 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 ALK mutations in 3% of ATCs and fusions in 3.6% of PDTCs. IDH1 mutation was identified in 1.25% of PDTCs but not in ATC. IDH2 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.
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