초록 ▼

◆ 연구내용 및 방법
- 역형성갑상선암 환자 1례 및 papillary 환자 2례로부터 cancer tissue의 확보 (cancer는 macro 분석으로 80%이상의 cancer cell이 포함되는 부분)
- Cancer tissue로부터 DNA의 추출 (macro-dissection), 역형성갑상선암의 경우 cancer cell heterogeneity를 연구하기 위해 tissue에서 3곳으로부터 DNA 추출, next generationsequencing 기술을 활용한 whole genome 및 whole exome

◆ 연구내용 및 방법
- 역형성갑상선암 환자 1례 및 papillary 환자 2례로부터 cancer tissue의 확보 (cancer는 macro 분석으로 80%이상의 cancer cell이 포함되는 부분)
- Cancer tissue로부터 DNA의 추출 (macro-dissection), 역형성갑상선암의 경우 cancer cell heterogeneity를 연구하기 위해 tissue에서 3곳으로부터 DNA 추출, next generationsequencing 기술을 활용한 whole genome 및 whole exome 분석 (총 8개의 sample)
- SNV calling의 concordance를 보기 위한 SNP chip analysis 수행
- Transcriptome 분석 (RNAseq) 및 Methylome 분석 (Bisulfite Seq)을 역형성갑상선암 환자에 대해 추가 수행
- Base calling, Data QC 후 SNP를 포함한 sequence variant analysis (In/del을 포함하는 Mutation, CNV, Fusion gene 등)
- 암종별 생명정보학 기술을 통하여 비교 분석하여 역형성갑상선암 특이적 유전자 변형 및 유전체의 특성 규명
- 공개된 데이터베이스(TCGA)의 갑상선암 유전체 데이터를 활용하여 역형성갑상선암에 나타나는 유전체 특성 발굴

Abstract ▼

Anaplastic thyroid cancer (ATC) is one of the most aggressive and rapidly progressive human cancer and has a very poor prognosis. Also, it shows high resistance to cancer treatments so that no effective treatment for ATC is available at present and virtually all patients die rapidly once the diagnos

Anaplastic thyroid cancer (ATC) is one of the most aggressive and rapidly progressive human cancer and has a very poor prognosis. Also, it shows high resistance to cancer treatments so that no effective treatment for ATC is available at present and virtually all patients die rapidly once the diagnosis is established. Although, the targeted treatment of genetic alteration has emerged as an extremely promising approach to human cancers such as BRAF in metastatic melanoma, it remains unclear that how common genetic alterations are involved in ATC tumorigenesis. In recent years, genome wide approaches were exploited to find genetic alterations associated with complex diseases including cancer. Especially, recent genomics technologies such as next generation sequencing (NGS) has provided comprehensive information of cancer genomics, especially for gene expression, sequence variations, copy number changes and epigenetic changes. Here, we tried to identify the genomic alterations in ATC using NGS technology. We performed whole genome sequencing, whole exom sequencing, RNA seq, Bisulfite seq and SNP chip analysis followed by intensive data analysis using div. bioinformatics tools. As results, we found ATC specific somatic variations (SNV, indel, CNV) and novel fusion genes. Also, we found ATC specific gene expression profiles and pathways including epigenetic alterations. By these genomic approaches, we are expecting to get a deep understanding of ATC specific molecular mechanism that is necessarily required for successful diagnosis and treatment of the aggressive cancer. Further, these efforts may facilitate the search for prognostic and predictive markers and new therapy targets for personalized medicine.

목차 Contents

• 목 차 ... 1
• 요약문 ... 2
• 한글요약문 ... 2
• Project Summary ... 4
• 1. 연구의 최종목표 ... 5
• 2. 연구의 내용 및 결과 ... 5
• 3. 연구결과 고찰 및 결론 ... 13
• 4. 연구성과 및 목표달성도 ... 15
• (1) 연구성과 ... 15
• (2) 목표달성도 ... 16
• 5. 연구결과의 활용계획 ... 17
• (1) 연구종료 2년후 예상 연구성과 ... 17
• (2) 연구성과의 활용계획 ... 18
• 6. 참고문헌 ... 18
• 7. 첨부서류 ... 18