Analysis of Exome Sequencing in Hepatocellular Carcinoma

Hepatocellular carcinoma (HCC) is the type of cancer difficult to classify and analyze despite the high occurrence, because it displays a high level of tumor heterogeneity with complex etiology. For unbiased analysis of HCC with diverse tumorigenic backgrounds, a genomewide study that does not target any specific target genes is needed. The mutation of known oncogenes was found from previous sequencing studies. The samples from HCC and surrounding liver samples were dissected from twelve HCC patients to investigate the pattern of tumor heterogeneity and analyze by subgroups, to be used in the integrated analysis including the whole exome sequencing to identify mutations and the gene expression profiling using microarray to identify differentially expressed genes. Two subgroups were obtained from gene expression studies, and divided according to the clinically diagnosed tumor stages. Class 1, showing low aggressiveness, displayed the high expression of metabolic activity, while Class 2, with high aggressiveness, displayed the high expression of genes modulating epigenetic regulation. From the mutation analysis 144 genes contained exonic, novel, and nonsynonymous somatic mutations in total. Two recurrently mutated genes, HMCN1 from immunoglobulin family and UNC80 comprising sodium ion channel, were found, and validated by Sanger sequencing. By the functional analysis of the set of mutated genes using gene ontology, genes regulating cell adhesion were mutated in both Class 1 and Class 2. Class 1 specifically included mutations in the genes regulating cellular development, while Class 2 genes for epigenetic regulations. As a result of determining the association between the cancer-specific mutations from exome sequencing and the chromosomal region with high epigenetic modifications, the mutated genes in the region with high histone H3k09 trimethylation displayed enrichment in the G-protein coupled receptor signaling and cell adhesion, and those with high histone H3k04 dimethylation had mutations in noncoding RNA processing and RNA metabolism in common. By the functional analysis from mutation studies of liver cancer, the profile of each subgroup was compared, and the functions related to tumor malignancy could be found.

Author dc:creator

• 조, 현우

Contributors dc:contributor

• 우, 현구
• 대학원 의생명과학과
• 201124158

• 간암
• 엑솜 염기서열 분석
• Microarray
• Gene ontology
• Hepatocellular carcinoma
• Exome sequencing

Language dc:language

ko

Identifier

http://dcoll.ajou.ac.kr:9080/dcollection/jsp/common/DcLoOrgPer.jsp?sItemId=000000013484
000000013484

OAI identifier oai:identifier

oai:repository.ajou.ac.kr:201003/8583