Deciphering the DNA methylation landscape of colorectal cancer in a Korean cohort

Seok-Byung Lim,Soobok Joe,Hyo-Ju Kim,Jong Lyul Lee,In Ja Park,Yong Sik Yoon,Chan Wook Kim,Jong Hwan Kim,Sangok Kim,Jin-Young Lee,Hyeran Shim,Hoang Bao Khanh Chu,Sheehyun Cho,Jisun Kang,Si-Cho Kim,Hong 생화학분자생물학회 2023 BMB Reports Vol.56 No.10

Aberrant DNA methylation plays a pivotal role in the onsetand progression of colorectal cancer (CRC), a disease with highincidence and mortality rates in Korea. Several CRC-associateddiagnostic and prognostic methylation markers have been identified;however, due to a lack of comprehensive clinical andmethylome data, these markers have not been validated in theKorean population. Therefore, in this study, we aimed to obtainthe CRC methylation profile using 172 tumors and 128 adjacentnormal colon tissues of Korean patients with CRC. Based onthe comparative methylome analysis, we found that hypermethylatedpositions in the tumor were predominantly concentratedin CpG islands and promoter regions, whereas hypomethylatedpositions were largely found in the open-sea region,notably distant from the CpG islands. In addition, we stratifiedpatients by applying the CpG island methylator phenotype(CIMP) to the tumor methylome data. This stratification validatedprevious clinicopathological implications, as tumors with highCIMP signatures were significantly correlated with the proximalcolon, higher prevalence of microsatellite instability status, andMLH1 promoter methylation. In conclusion, our extensive methylomeanalysis and the accompanying dataset offers valuableinsights into the utilization of CRC-associated methylation markersin Korean patients, potentially improving CRC diagnosis andprognosis. Furthermore, this study serves as a solid foundationfor further investigations into personalized and ethnicity-specificCRC treatments.

A highly annotated whole-genome sequence of a Korean individual

Kim, Jong-Il,Ju, Young Seok,Park, Hansoo,Kim, Sheehyun,Lee, Seonwook,Yi, Jae-Hyuk,Mudge, Joann,Miller, Neil A.,Hong, Dongwan,Bell, Callum J.,Kim, Hye-Sun,Chung, In-Soon,Lee, Woo-Chung,Lee, Ji-Sun,Seo, Macmillan Publishers Limited. All rights reserved 2009 Nature Vol.460 No.7258

Recent advances in sequencing technologies have initiated an era of personal genome sequences. To date, human genome sequences have been reported for individuals with ancestry in three distinct geographical regions: a Yoruba African, two individuals of northwest European origin, and a person from China. Here we provide a highly annotated, whole-genome sequence for a Korean individual, known as AK1. The genome of AK1 was determined by an exacting, combined approach that included whole-genome shotgun sequencing (27.8× coverage), targeted bacterial artificial chromosome sequencing, and high-resolution comparative genomic hybridization using custom microarrays featuring more than 24 million probes. Alignment to the NCBI reference, a composite of several ethnic clades, disclosed nearly 3.45 million single nucleotide polymorphisms (SNPs), including 10,162 non-synonymous SNPs, and 170,202 deletion or insertion polymorphisms (indels). SNP and indel densities were strongly correlated genome-wide. Applying very conservative criteria yielded highly reliable copy number variants for clinical considerations. Potential medical phenotypes were annotated for non-synonymous SNPs, coding domain indels, and structural variants. The integration of several human whole-genome sequences derived from several ethnic groups will assist in understanding genetic ancestry, migration patterns and population bottlenecks.

Comprehensive RNA-sequencing analysis of colorectal cancer in a Korean cohort

Jaeim Lee,Jong-Hwan Kim,Hoang Bao Khanh Chu,Seong-Taek Oh,Sung-Bum Kang,Sejoon Lee,Duck-Woo Kim,Heung-Kwon Oh,Ji-Hwan Park,Jisu Kim,Jisun Kang,Jin-Young Lee,Sheehyun Cho,Hyeran Shim,Hong Seok Lee,Seon Korean Society for Molecular and Cellular Biology 2024 Molecules and cells Vol.47 No.3

Considering the recent increase in the number of colorectal cancer (CRC) cases in South Korea, we aimed to clarify the molecular characteristics of CRC unique to the Korean population. To gain insights into the complexities of CRC and promote the exchange of critical data, RNA-sequencing analysis was performed to reveal the molecular mechanisms that drive the development and progression of CRC; this analysis is critical for developing effective treatment strategies. We performed RNA-sequencing analysis of CRC and adjacent normal tissue samples from 214 Korean participants (comprising a total of 381 including 169 normal and 212 tumor samples) to investigate differential gene expression between the groups. We identified 19,575 genes expressed in CRC and normal tissues, with 3,830 differentially expressed genes (DEGs) between the groups. Functional annotation analysis revealed that the upregulated DEGs were significantly enriched in pathways related to the cell cycle, DNA replication, and IL-17, whereas the downregulated DEGs were enriched in metabolic pathways. We also analyzed the relationship between clinical information and subtypes using the Consensus Molecular Subtype (CMS) classification. Furthermore, we compared groups clustered within our dataset to CMS groups and performed additional analysis of the methylation data between DEGs and CMS groups to provide comprehensive biological insights from various perspectives. Our study provides valuable insights into the molecular mechanisms underlying CRC in Korean patients and serves as a platform for identifying potential target genes for this disease. The raw data and processed results have been deposited in a public repository for further analysis and exploration.

Comprehensive RNA-sequencing analysis of colorectal cancer in a Korean cohort

Kil-yong Lee,Jaeim Lee,Jong Hwan Kim,Hoang Bao Khanh Chu,Seong-Taek Oh,Sung-Bum Kang,Sejoon Lee,Duck-Woo Kim,Heung-Kwon Oh,Ji-Hwan Park,Ji-Su Kim,Jisun Kang,Jin-Young Lee,Sheehyun Cho,심혜란,Hong Seok Le 한국분자세포생물학회 2024 Molecules and cells Vol.47 No.1

Considering the recent increase in the number of colorectal cancer (CRC) cases in South Korea, we aimed to clarify the molecular characteristics of CRC unique to the Korean population. To gain insights into the complexities of CRC and promote the exchange of critical data, RNA-sequencing analysis was performed to reveal the molecular mechanisms that drive the development and progression of CRC; this analysis is critical for developing effective treatment strategies. We performed RNA-sequencing analysis of CRC and adjacent normal tissue samples from 214 Korean participants (comprising a total of 381 including 169 normal and 212 tumor samples) to investigate differential gene expression between the groups. We identified 19,575 genes expressed in CRC and normal tissues, with 3,830 differentially expressed genes (DEGs) between the groups. Functional annotation analysis revealed that the upregulated DEGs were significantly enriched in pathways related to the cell cycle, DNA replication, and IL-17, whereas the downregulated DEGs were enriched in metabolic pathways. We also analyzed the relationship between clinical information and subtypes using the Consensus Molecular Subtype (CMS) classification. Furthermore, we compared groups clustered within our dataset to CMS groups and performed additional analysis of the methylation data between DEGs and CMS groups to provide comprehensive biological insights from various perspectives. Our study provides valuable insights into the molecular mechanisms underlying CRC in Korean patients and serves as a platform for identifying potential target genes for this disease. The raw data and processed results have been deposited in a public repository for further analysis and exploration.

TIARA: a database for accurate analysis of multiple personal genomes based on cross-technology

Hong, Dongwan,Park, Sung-Soo,Ju, Young Seok,Kim, Sheehyun,Shin, Jong-Yeon,Kim, Sujung,Yu, Saet-Byeol,Lee, Won-Chul,Lee, Seungbok,Park, Hansoo,Kim, Jong-Il,Seo, Jeong-Sun Oxford University Press 2011 Nucleic acids research Vol.39 No.1

<P>High-throughput genomic technologies have been used to explore personal human genomes for the past few years. Although the integration of technologies is important for high-accuracy detection of personal genomic variations, no databases have been prepared to systematically archive genomes and to facilitate the comparison of personal genomic data sets prepared using a variety of experimental platforms. We describe here the Total Integrated Archive of Short-Read and Array (TIARA; http://tiara.gmi.ac.kr) database, which contains personal genomic information obtained from next generation sequencing (NGS) techniques and ultra-high-resolution comparative genomic hybridization (CGH) arrays. This database improves the accuracy of detecting personal genomic variations, such as SNPs, short indels and structural variants (SVs). At present, 36 individual genomes have been archived and may be displayed in the database. TIARA supports a user-friendly genome browser, which retrieves read-depths (RDs) and log2 ratios from NGS and CGH arrays, respectively. In addition, this database provides information on all genomic variants and the raw data, including short reads and feature-level CGH data, through anonymous file transfer protocol. More personal genomes will be archived as more individuals are analyzed by NGS or CGH array. TIARA provides a new approach to the accurate interpretation of personal genomes for genome research.</P>

Epigenetic insights into colorectal cancer: comprehensive genome-wide DNA methylation profiling of 294 patients in Korea

Soobok Joe,Jinyong Kim,Jinyoung Lee,Jongbum Jeon,Iksu Byeon,Sae-Won Han,Seung-Bum Ryoo,Kyu-Joo Park,Sang-Hyun Song,Sheehyun Cho,Hyeran Shim,Hoang Bao Khanh Chu,Jisun Kang,Hong Seok Lee,DongWoo Kim,You 생화학분자생물학회 2023 BMB Reports Vol.56 No.10

DNA methylation regulates gene expression and contributes totumorigenesis in the early stages of cancer. In colorectal cancer(CRC), CpG island methylator phenotype (CIMP) is recognizedas a distinct subset that is associated with specific molecularand clinical features. In this study, we investigated the genomewideDNA methylation patterns among patients with CRC. The methylation data of 1 unmatched normal, 142 adjacentnormal, and 294 tumor samples were analyzed. We identified40,003 differentially methylated positions with 6,933 (79.8%)hypermethylated and 16,145 (51.6%) hypomethylated probesin the genic region. Hypermethylated probes were predominantlyfound in promoter-like regions, CpG islands, and N shore sites;hypomethylated probes were enriched in open-sea regions. CRC tumors were categorized into three CIMP subgroups, with90 (30.6%) in the CIMP-high (CIMP-H), 115 (39.1%) in theCIMP-low (CIMP-L), and 89 (30.3%) in the non-CIMP group. The CIMP-H group was associated with microsatellite instabilityhightumors, hypermethylation of MLH1, older age, and rightsidedtumors. Our results showed that genome-wide methylationanalyses classified patients with CRC into three subgroupsaccording to CIMP levels, with clinical and molecular featuresconsistent with previous data.

The First Korean Case of VEXAS Syndrome Caused by a UBA1 Somatic Variant

Yoon Jihoon G.,Lee Seungbok,Kim Sheehyun,Kim Man Jin,Chang Yoon Hwan,Park Jin Kyun,Shin Dong-Yeop,Moon Jangsup 대한진단검사의학회 2023 Annals of Laboratory Medicine Vol.43 No.2