Mutational analysis of the GNA11, MMP27, FGD1, TRRAP and GRM3 genes in thyroid cancer

Abstract

Frequent somatic mutations in the GNA11, matrix metalloproteinase (MMP)27, FGD1, TRRAP and GRM3 genes have been reported in various types of human cancer, but whether these genes are mutated in thyroid cancer is not known. In the present study, a mutational analysis of these genes was performed in thyroid cancer cell lines and thyroid cancer samples. No GNA11 mutations were identified in the papillary thyroid cancer (PTC), follicular thyroid cancer (FTC) and anaplastic thyroid cancer (ATC) samples. Additionally, no mutations were identified in the MMP27 gene, although three synonymous [C351T (N117N), C1089T (S363S) and G1227A (G409G)] single nucleotide polymorphisms (SNPs) were observed infrequently in ATC. No mutations were detected in the FGD1 gene, but two infrequent synonymous [T2091C (T697T) and A2136G (P712P)] SNPs were observed in PTC. Furthermore, no mutations were identified in TRRAP and GRM3, although a frequent synonymous SNP [G1323A (T441T)] and infrequent non-synonymous SNP [G1424A (G475D)] of GRM3 were observed in PTC. No mutation of these genes was observed in 12 cell lines derived from various types of thyroid cancer. The present study reports for the first time the mutational status of the GNA11, MMP27, FGD1, TRRAP and GRM3 genes in thyroid cancer. No mutations were identified in these genes in the various types and cell lines of thyroid cancer. Therefore, unlike in other types of cancer, mutations in these genes are absent or uncommon in thyroid cancer.

Keywords: FGD1; GNA11; GRM3; MMP27; TRRAP; mutation; thyroid cancer.

Figure 1.

Detection of MMP27, FGD1 and GRM3 mutations. (A) Sequencing results are shown with a representative sense sequence profile of SNPs (N117N, S363S and G409G) detected in exons 3, 8 and 9 of the MMP27 gene. Arrows indicate mutated nucleotides. (B) Schematic diagram of domains of the MMP27 protein showing three SNPs (N117N, S363S and G409G) identified in thyroid cancer. (C) Sequencing results are shown with a representative sense sequence profile of SNPs (T697T and P712P) detected in exon 14 of the FGD1 gene. Arrows indicate mutated nucleotides. (D) Schematic diagram of domains of the FGD1 protein showing two SNPs (T697T and P712P) identified in thyroid cancer. (E) Sequencing results are shown with a representative sense sequence profile of two SNPs (T441T and G475D) detected in exon 3 of the GRM3 gene. Arrows indicate mutated nucleotides. The nucleotide, amino acid alteration and tumor number are indicated above the arrows. Nucleotide numbers refer to the position within the coding sequences, where position 1 corresponds to the first position of the initiation codon. All the samples were sequenced in two repeated examinations with independent PCR by forward and reverse primers. MMP, matrix metalloproteinase; SNPs, single nucleotide polymorphisms.