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간암의 DNA 복제수 의존성 유전 발현 변이 발굴
- Alternative Title
- SO MEE KWON
- Author(s)
- Kwon, So Mee
- Alternative Author(s)
- SO MEE KWON
- Advisor
- 백은주, 우현구
- Department
- 일반대학원 의학계열
- Publisher
- The Graduate School, Ajou University
- Publication Year
- 2014-02
- Language
- eng
- Keyword
- HCC (Hepatocellular carcinoma); DNA copy number; integrative analysis; IER3; biomarker; HCC subtypes; 6p21-24; transcriptional deregulation
- Alternative Abstract
- In recent years, cancer heterogeneity, which is essentially inherent in various types of cancer, has been of interest to the cancer genome research. Many studies using various approaches have tried to solve the conundrum of so-called cancer heterogeneity. However, even though many successes have been earned in this area using the genomic analysis, the identification of precise cancer subtypes, which can be informative and useful from the biological and clinical point of view, still remains a challenge. Among the many trials, the multi-layered genomic profiles analysis, in which the genomic copy numbers and gene expression profiles are analyzed by the integrative way to define the chromosomal regions with both genomic copy number variation and concomitant transcriptional deregulation, is posited to provide a promising strategy to identify driver targets. Here, the integrative analysis of the DNA copy numbers and gene expression profiles of hepatocellular carcinoma (HCC) was performed. By comparing DNA copy numbers in HCC subtypes, which have been previously defined based on gene expression pattern, it was found that the HCC subtype showing aggressive phenotype without expressing stemness-related genes had DNA copy number alteration with concordant gene expression changes in the specific chromosomal area at 6p21-24. Among the genes residing at 6p21-24, IER3 was identified as a potential driver. The clinical utility of IER3 copy numbers was demonstrated by validating its clinical correlation in the independent cohorts. In addition, short hairpin RNA-mediated knock-down experiment revealed the functional relevance of IER3 in liver cancer progression. In conclusion, the results of this study suggest that genomic copy number alterations with transcriptional deregulation at 6p21-24 identify an aggressive HCC phenotype and a novel functional biomarker.
- Fulltext
- Appears in Collections:
- Graduate School of Ajou University > Department of Medicine > 4. Theses(Ph.D)
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