NIS Mutations In Patients With Differentiated Thyroid Cancer

Purpose:In recent years,thyroid cancer has grown rapidly and became one of the fastest growing solid tumors.Differentiated thyroid carcinomas(DTC)account for 85-90% of thyroid carcinomas(TC)and the majority of growth rate of thyroid cancer.With the development of molecular biology,the study of thyroid cancer at the molecular level has been paid increasing attention.So far,Braf gene mutation,Ret / PTC recombination,Ras point mutation,PAX8/PPAR? gene recombination and Na+/ISymporter(NIS)gene mutation have been found a certain relationship with thyroid carcinoma.NIS plays a key role in thyroid iodine function.In the process of thyroid cancer differentiation,NIS mutation may lead to its dedifferentiation,which in turn loss of iodine function and will be ineffective in the radiation iodine treatment.This study was to study and analyze the types and characteristics of NIS mutations in patients with differentiated thyroid carcinoma,and to explore the relationship between gene type and phenotype in order to provide some theory for gene diagnosis,gene therapy and prognosis of DTC patients.Methods: According to the selection criteria that patients with the history of thyroid tumors only and did not receive preoperative thyroid radiotherapy were included.A total of 100 patients with DTC who underwent surgical treatment of thyroid carcinoma in the Affiliated Hospital of Qingdao University from 2016.04 to 2016.07 and confirmed by two pathologists were enrolled.Genomic DNA was extracted from cancer tissues and normal tissues.PCR amplification and direct sequencing of the NIS gene exon and a number of near intron gene mutation detection was carried out after DNA was extracted.The gene frequency of the detected mutations was verified by chi-square test,and p <0.5 was a statistically significant difference between cancer group and normal tissue group.Results: One missense mutation(c.1663C> T,p.Arg555Cys)located in exon 14 of the NIS was found in one patient.One synonymous gene mutation(c.1571 C> T,p.Leu 408 =)located in exon 10 of the NIS was found in 2 patients with cancer.In one patient,a synonym gene mutation(c.1224C> T,p.Leu408 =)was found in the exon 8 of the NIS.A SNP: rs740695(c.-1207 C & gt;T)was found from the first intron of patients been numbered 9,13,27,35,41.In the patient numbered No.1,a SNP mutation site of the 5th intron was found to be rs185045651(c.332 + 52G> A).A SNP mutation rs182064161(c.839 + 11C> T)was found in the 6th intron in patients numbered 4,18,46,61,89.A SNP mutation rs148626179(c.1767 + 23A> C)was found in the 14 th intron in patients been numbered 10,23,24,58.A SNP rs4808709(1767 + 29A> G)was also found in the 14 th intron of patients been numbered 31 and 86.No mutations were found in other cancer tissues and in all normal tissues.There was no significant difference in the frequency of gene mutation between the two groups by chi-square test(p>0.05).Conclusions: The frequency of cancer tissue group and normal tissue group gene mutation has no significant difference by chi-square test.When the risk analysis was performed by the polyphen-2 procedure to detect missense mutations(c.1663C> T,p.Arg555Cys),its value is 1 and shows damaging.When runed by SIFT,its value is 0 and shows damaging.The patient is a 51 year old woman,with PTC,tumor diameter of 0.7 cm,cervical lymph node metastasis and focal foci.Genotype and phenotypic relationship is not obvious.NIS mutations may not be associated with differentiated thyroid carcinoma in Qingdao.The missense mutation may play a role in thyroid iodine development,and the specific function remains to be verified by the next step.The two synonymous mutations(c.1571 C> T,p.Leu 408 =)and(c.1224C> T,p.Leu408 =),although the codon changes,both codons are encoded by leucine.The relationship between genotype and phenotype is unclear and remains to be studied further.