Whole transcriptome analysis of papillary thyroid carcinoma using massively parallel sequencing : 차세대 염기서열 분석을 이용한 갑상선 유두암 전사체 분석

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의과대학 의과학과
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서울대학교 대학원
papillary thyroid carcinomatranscriptome sequencingmutation profilingexpression profilingdriver candidate
학위논문 (박사)-- 서울대학교 대학원 : 의과학과, 2014. 2. 서정선.
Thyroid cancer is one of the most prevalent cancers worldwide, and papillary thyroid carcinoma (PTC) accounts for >80% of all thyroid cancers. There have been several approaches for molecular diagnostics for PTC
however, its genetic background still needs to be screened in a broad spectrum for each ethnicity. Here we conducted RNA sequencing for 63 PTC and 42 paired-normal tissues in Korean patients, along with five follicular thyroid carcinoma (FTC) and two follicular adenoma (FA) samples. In gene fusion analysis, we discovered five fusion mutations including two novel (EZR-ERBB4 and PAX8-GLIS3) and three previously identified fusions (CCDC6-RET, ETV6-NTRK3, and PAX8-PPARG). EZR-ERBB4 was shown in follicular variant PTC, and the predicted fusion product includes a protein tyrosine kinase domain. Every fusion mutation above was shown once among our study subjects. When point mutations were screened, BRAF V600E, HRAS Q61K/R, and NRAS Q61R mutations, which are well-established mutations in PTC, were detected in 74.6%, 3.18%, and 1.59% of PTC samples, respectively. In addition, we discovered a novel driver candidate, DICER1 E1813Q, in one patient. In total, we suggested driver mutations in 87.31% of PTC patients, and cancer outlier genes NTRK3 and NRAS were also shown in two and one driver-unidentified samples respectively. Lastly, we have shown that expression profiles of tumor samples were clustered into four groups
three of them enriched with BRAF V600E mutations and PTC, and the other with NRAS, HRAS, DICER1 mutations and FTC/FA. In this study, we thoroughly explored the transcriptome of PTC in Korean patients using massively parallel sequencing and demonstrated a high correlation between mutation and expression profiles. As a result, we suggested some novel genes and pathways involved in PTC development, which would lead to the more exact molecular diagnostics and targeted treatment.
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College of Medicine/School of Medicine (의과대학/대학원)Dept. of Biomedical Sciences (대학원 의과학과)Theses (Ph.D. / Sc.D._의과학과)
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