초록 ▼

○ 연구결과 : ① 한국인 갑상선종양에서 Gs a , ras, p53 돌연변이와 ret/PTC 재배열을 검색하고 MDM2, Bcl-2 단백군도 검출하였다. 상기 결과에서 유전적 이상 소견을 나타내지
갑상선종양을 대상으로 유전자 단위의 이상을 검색하고자 microsattelite marker allelotyping과 comparative genomic hyblidization을 시행하였고， 정상 갑상선조직과 갑상선 종양간에 differential display PCR을 하여 종양특이 유전자산물을 검출하였다.② 분화 갑상선암에서

○ 연구결과 : ① 한국인 갑상선종양에서 Gs a , ras, p53 돌연변이와 ret/PTC 재배열을 검색하고 MDM2, Bcl-2 단백군도 검출하였다. 상기 결과에서 유전적 이상 소견을 나타내지
갑상선종양을 대상으로 유전자 단위의 이상을 검색하고자 microsattelite marker allelotyping과 comparative genomic hyblidization을 시행하였고， 정상 갑상선조직과 갑상선 종양간에 differential display PCR을 하여 종양특이 유전자산물을 검출하였다.② 분화 갑상선암에서 방사성옥소 치료 반응인자 및 예후인자로서 hNIS mRNA를 갑상선종양에서 검출하였고 갑상선 내 유두암 조직과 전이 유두암 조직간의 hNIS mRNA 발현의 차이를 알아보았으며 소량의 조직에서 상기 mRNA를 검출할 수 있는 quantitative RT-PCR 법을 구축하였다. ③ p53 돌연변이가 있는 미분화암을 대상으로 retrovirus를 이용한 p53 유전자 치료법을 시도하였고 방사성옥소를 섭취하지 않는 분화 전이 갑상선암을 대상으로 adenovirus를 이용한 hNIS 유전자 치료방법을 개발하는 기초작업을 하였다.

Abstract ▼

Recent advances in thyroid tumorigenesis have assisted understanding of the appearance of different functions and histologies originated from thyroid follicular cells. Prevalence of the genetic alterations have been reported to vary widely in different geographical areas. Also there are significant

Recent advances in thyroid tumorigenesis have assisted understanding of the appearance of different functions and histologies originated from thyroid follicular cells. Prevalence of the genetic alterations have been reported to vary widely in different geographical areas. Also there are significant proportions of thyroid tumors which do not have known genetic alterations and the causes still not defined. Molecular pathogenesis of thyroid tumor in Korean population have not been studied. The limitations on present clinical practice of thyroid tumors are expected to be solved by the understanding of molecular pathogenesis. This study was performed ① to have base line data of prevalence of known genetic alterations in thyroid tumors of Korean population, ② to verify the characteristics of tumors without known genetic alterations on genomic scale, ③ to establish an index-human sodium iodide symporter(hNIS) mRNA measurement in thyroid cancers-for the prediction of therapeutic response to radioiodine, ④ to develop new treatment modalities-hNIS gene therapy for hNIS(-) metastatic differentiated thyroid carcinoma, p53 gene therapy for anaplastic thyroid carcinoma with p53 mutation, where effective treatments are not present.
Under the heading of 'Prevaleces of Gs a, ras, p53 mutations and ret/PTC rearrangement in differentiated thyroid tumours in a Korean population', we defined ret/PTC rearrangement, Gs a, ras and p53 mutations are relatively rare in differentiated thyroid neoplasia from a Korean population, which may reflect genetic and environmental differences from patients in countries with high prevalences. P53 protein over-expression was noted in 13.3% of papillary carcinoma cases without p53 mutation and was not significantly related to MDM2 and Bcl-2 expression. As an extension of the above study, Bcl-2 family protein expressions in thyroid tumors were also evaluated. Under the title of 'Microsatellite marker allelotyping and comparative genomic hybridization in papillary thyroid carcinoma and follicular adenoma', abnormality on whole genomic scale was evaluated where hot spot of LOH was not observed in micro satellite allelotyping even with significant micro satellite instabilities (50, 60% each). Neither of conunon chromosomal change was observed in CGH study, suggesting unbalanced translocation or gene amplification more than 5-10 Mb may not be involved in the genetic alterations of papillary carcinoma. With the title of 'Expressions of human sodium iodide symporter mRNA in primary and metastatic papillary thyroid carcinomas', the role of hNIS mRNA measurement in clinical practice was evaluated where 13% of papillary carcinoma(3/23) didn't express hNIS mRNA. The levels of hNIS mRNA, when expressed, were variable and correlate with TSH-receptor mRNA levels.
No correlation was found ill hNIS mRNA expression between primary and lymph node metastatic tissue, suggesting the measurements of hNIS mRNA level in primary tissues may not predict therapeutic response to radioactive iodine. Finally, with the heading of 'Growth and chemosensitivity of human papillary thyroid cancer cell line(NPA) transfected with p53 gene', tumor growth inhibition and increased sensltlvlty adriamvcin chemosensitivity were observed by p53 transfection into NPA cellsCin vitro and in vivo) to suggest the treatment modality could be beneficial in the treatment of p53 mutation positive thyroid cancers. Also increased RAIU was observed in hNIS(-) cells by transfection of p△ ACMVp(A)+hNIS vectorCin vitro).