A5000053481- Cancer Genomics and Diagnostics
- Renal and related cancers
- RNA modifications and cancer
- Epigenetics and DNA Methylation
- Genetic factors in colorectal cancer
- RNA and protein synthesis mechanisms
- RNA Research and Splicing
- Single-cell and spatial transcriptomics
- Bioinformatics and Genomic Networks
- Cancer-related molecular mechanisms research
- Cancer Immunotherapy and Biomarkers
- Genomics and Rare Diseases
- Acute Myeloid Leukemia Research
- Genomic variations and chromosomal abnormalities
- Hematopoietic Stem Cell Transplantation
- Ubiquitin and proteasome pathways
- T-cell and B-cell Immunology
- DNA Repair Mechanisms
- vaccines and immunoinformatics approaches
- Sarcoma Diagnosis and Treatment
- Lung Cancer Treatments and Mutations
- Neurofibromatosis and Schwannoma Cases
- Ethics and Legal Issues in Pediatric Healthcare
- Testicular diseases and treatments
- Endoplasmic Reticulum Stress and Disease
Wellcome Sanger Institute
2019-2025
University of Ulsan
2025
Asan Medical Center
2025
Ulsan College
2025
Korea Advanced Institute of Science and Technology
2009-2021
Samsung Medical Center
2011-2018
Korea Institute of Brain Science
2017
National Cancer Center
2013-2015
University of California, San Diego
2009-2013
Sungkyunkwan University
2011
Abstract Mitotic cell division increases tumour mutation burden and copy number load, predictive markers of the clinical benefit immunotherapy. Cell correlates also with genomic demethylation involving methylation loss in late-replicating partial domains. Here we find that immunomodulatory pathway genes are concentrated these domains transcriptionally repressed demethylated tumours CpG island promoter hypermethylation. Global correlated immune evasion signatures independently aneuploidy....
Abstract Age-related change in human haematopoiesis causes reduced regenerative capacity 1 , cytopenias 2 immune dysfunction 3 and increased risk of blood cancer 4–6 but the reason for such abrupt functional decline after 70 years age remains unclear. Here we sequenced 3,579 genomes from single cell-derived colonies haematopoietic cells across 10 subjects 0 to 81 age. Haematopoietic stem or multipotent progenitors (HSC/MPPs) accumulated a mean 17 mutations per year birth lost 30 base pairs...
Inflammatory bowel disease (IBD) is a chronic inflammatory associated with increased risk of gastrointestinal cancers. We whole-genome sequenced 446 colonic crypts from 46 IBD patients and compared these to 412 41 non-IBD controls our previous publication on the mutation landscape normal colon. The average rate affected epithelial cells 2.4-fold that healthy colon, this increase mostly driven by acceleration mutational processes ubiquitously observed in In contrast where clonal expansions...
Significance Unique among the large number of noncoding RNA species, pericentromeric human satellite II (HSATII) repeat is massively expressed in a broad set epithelial cancers but nearly undetectable normal tissues. Here, we show that deregulation HSATII expression tightly linked to growth under nonadherent conditions, and uncover an unexpected mechanism by which RNA-derived DNA (rdDNA) leads progressive elongation regions tumors. The remarkable specificity overexpression cancers, together...
Abstract Background It is crucial to unravel molecular determinants of responses immune checkpoint blockade (ICB) therapy because only a small subset advanced non-small cell lung cancer (NSCLC) patients responds ICB therapy. Previous studies were concentrated on genomic and transcriptomic markers (e.g., mutation burden gene expression). However, these are not sufficient accurately predict response Results Here, we analyzed DNA methylomes 141 NSCLC samples subjected (i.e., anti-programmed...
Abstract Cellular DNA damage caused by reactive oxygen species is repaired the base excision repair (BER) pathway which includes glycosylase MUTYH. Inherited biallelic MUTYH mutations cause predisposition to colorectal adenomas and carcinoma. However, mechanistic progression from germline MUTYH-Associated Polyposis (MAP) incompletely understood. Here, we sequence normal tissue DNAs 10 individuals with MAP. Somatic substitution mutation rates in intestinal epithelial cells were elevated 2...
Abstract APOBEC mutational signatures SBS2 and SBS13 are common in many human cancer types. However, there is an incomplete understanding of its stimulus, when it occurs the progression from normal to cell enzymes responsible. Here we whole-genome sequenced 342 microdissected epithelial crypts small intestines 39 individuals found that SBS2/SBS13 mutations were present 17% crypts, more frequent than most other tissues. Crypts with often had immediate crypt neighbors without SBS2/SBS13,...
Abstract Gene therapy (GT) provides a potentially curative treatment option for patients with sickle cell disease (SCD); however, the occurrence of myeloid malignancies in GT clinical trials has prompted concern, several postulated mechanisms. Here, we used whole-genome sequencing to track hematopoietic stem cells (HSCs) from six SCD at pre- and post-GT time points map somatic mutation clonal landscape gene-modified unmodified HSCs. Pre-GT, phylogenetic trees were highly polyclonal burdens...
Abstract Somatic variants accumulate in non-malignant tissues with age. Functional variants, leading to clonal advantage of hepatocytes, the liver patients acquired chronic disease (CLD). Whether somatic are common CLD from differing etiologies is unknown. We analyzed genetic alpha-1 antitrypsin (A1AT) deficiency or hemochromatosis. show that SERPINA1 , gene encoding A1AT, strongly selected for A1AT deficiency, evidence convergent evolution. Acquired clustered at carboxyl terminus...
The utilization of archived, formalin-fixed paraffin-embedded (FFPE) tumor samples for massive parallel sequencing has been challenging due to DNA damage and contamination with normal stroma. Here, we perform whole genome isolated from two triple-negative breast cancer tumors archived >11 years as 5 µm FFPE sections matched germline DNA. show differing amounts damaged reads revealed relatively high alignment mismatch rates enriched C·G > T·A substitutions compared samples. This increase in...
Annexin A2 (ANXA2) expression is highly upregulated in many types of cancer. Although cell surface localization ANXA2 has been reported to have a critical role the progression and metastasis variety tumors, including pancreatic cancer, biological intracellular not fully understood. Herein was investigated cancer line. We first determined whether involved NF-κB signaling pathways. bound p50 subunit calcium-independent manner, ANXA2-p50 complex translocated into nucleus. Furthermore, increased...
Previous studies studying mis-splicing mutations were based on exome data and thus our current knowledge is largely limited to exons the canonical splice sites. To comprehensively characterise intronic mutations, we analysed 1134 pan-cancer whole genomes transcriptomes together with 3022 normal control samples. The ratio-based splicing analysis resulted in 678 somatic 46% residing deep introns. Among 309 single nucleotide variants, 245 altered core codes, 38% activating cryptic sites, 12%...
L1 retrotransposons can pose a threat to genome integrity. The host has evolved restrict replication. However, mechanisms underlying propagation out of the surveillance remains unclear. Here, we propose an evolutionary survival strategy L1, which exploits RNA m6A modification. We discover that 'writer' METTL3 facilitates retrotransposition, whereas 'eraser' ALKBH5 suppresses it. essential cluster is located on 5' UTR serves as docking site for eukaryotic initiation factor 3 (eIF3), enhances...
Abstract Allogeneic haematopoietic cell transplantation (HCT) replaces the stem cells responsible for blood production with those from a donor 1,2 . Here, to quantify dynamics of long-term engraftment, we sequenced genomes 2,824 single-cell-derived colonies ten donor–recipient pairs taken 9–31 years after HLA-matched sibling HCT 3 With younger donors (18–47 at transplant), 5,000–30,000 had engrafted and were still contributing haematopoiesis time sampling; estimates tenfold lower older...
The epigenetic landscape of cancer is regulated by many factors, but primarily it derives from the underlying genome sequence. Chromothripsis a catastrophic localized shattering event that drives, and often initiates, evolution. We characterized five esophageal adenocarcinoma organoids with chromothripsis using long-read sequencing transcriptome epigenome profiling. Complex structural variation subclonal variants meant haplotype-aware de novo methods were required to generate contiguous...
// Hyunchul Jung 1, 4, * , Hae Yong Yoo 2, Seung Ho Lee Sohyun Shin 3, Sang Cheol Kim Sejoon Je-Gun Joung Jae-Yong Nam Daeun Ryu Jae Won Yun 5, Kyoon Choi Ambarnil Ghosh Kyeong Kyu Seok Jin 6, Seog Woong-Yang Park 1 and Young Hyeh Ko 3 Department of Bio Brain Engineering, Korea Advanced Institute Science Technology (KAIST), Daejeon, Republic 2 Health Sciences Technology, Samsung for Sungkyunkwan University, Seoul, Pathology, Medical Center, University School Medicine, 4 Genome Institute,...
Long interspersed nuclear element-1 (LINE-1 or L1) retrotransposons are normally suppressed in somatic tissues mainly due to DNA methylation and antiviral defense. However, the mechanism suppress L1s may be disrupted cancers, thus allowing act as insertional mutagens cause genomic rearrangement instability. Whereas frequency of L1 insertions varies greatly among individual tumors, much remains learned about underlying genetic, cellular, environmental factors. Here, we report multiple...
Neoantigen burden is regarded as a fundamental determinant of response to immunotherapy. However, its predictive value remains in question because some tumours with high neoantigen load show resistance. Here, we investigate our patient cohort together public by algorithms for the modelling peptide-MHC binding and inter-cohort genomic prediction therapeutic We first attempt predict MHC-binding peptides at accuracy convolutional neural networks. Our outperforms previous methods > 70% test...
<title>Abstract</title> Allogeneic haematopoietic cell transplantation (HCT) replaces the stem cells responsible for blood production with those harvested from a donor, and is received by 40,000 patients worldwide each year. To quantify dynamics of long-term engraftment, we sequenced whole genomes 2,824 single-cell-derived colonies samples 10 donor-recipient pairs taken 9-31 years after HLA-matched sibling HCT. With younger donors, 10,000–50,000 had engrafted were still contributing to...
Abstract In developed countries, ∼10% of individuals are exposed to systemic chemotherapy for cancer and other diseases. Many chemotherapeutic agents act by increasing DNA damage in cells, triggering cell death. However, there is limited understanding the extent long-term consequences collateral normal tissues. To investigate impact on mutation burdens population structure a tissue we sequenced blood genomes from 23 individuals, aged 3–80 years, treated with range regimens. Substantial...
Dear Editor, Glioblastoma (GBM), the most aggressive malignant tumour, is increasingly treated with immunotherapy.1-3 The stimulator of interferon genes (STING) pathway4 key to tumour immunity and a studied target for immunotherapy.5 This study explores immune landscape GBM, focusing on spatial relationships between tumour-associated cells (TAICs)6 STING-expressing cells, uncovering patterns linked prognosis. We 14 recurrent GBM patients using protein composition Gene Ontology (GO) analysis...
<div>Abstract<p>Approximately 10% of children with cancer harbor a mutation in predisposition gene. In the kidney Wilms tumor, prevalence is as high 30%. Certain predispositions are associated defined histological and clinical features, suggesting differences tumorigenesis. To investigate this, we assembled cohort 137 whom 71 had pathogenic germline or mosaic variant. We examined 237 neoplasms (including two secondary leukemias), utilizing whole-genome sequencing, RNA genome-wide...
<p>Contains Supplementary Figures 1-9. Figure 1 shows age of diagnosis children and indel burden rearrangement for tumours from predisposed versus those with sporadic disease. 2 genomic evidence novel predispositions. 3 global methylation patterns. 4 differential gene expression. 5 mutational signatures. 6 histological subtypes across predispositions somatic drivers. 7 polyclonal clonal enrichment 11p LOH in normal kidneys. 8 phylogenies multiple neoplasms either WT1 or TRIM28 9 non...