A5028785394- Cancer Genomics and Diagnostics
- Genetic factors in colorectal cancer
- Colorectal Cancer Treatments and Studies
- Genomics and Rare Diseases
- Radiomics and Machine Learning in Medical Imaging
- Pluripotent Stem Cells Research
- Thyroid Cancer Diagnosis and Treatment
- DNA Repair Mechanisms
- Renal and related cancers
- PARP inhibition in cancer therapy
- Cancer, Hypoxia, and Metabolism
- Chromosomal and Genetic Variations
- Lung Cancer Treatments and Mutations
- Health Systems, Economic Evaluations, Quality of Life
- Bioinformatics and Genomic Networks
- Mitochondrial Function and Pathology
- CRISPR and Genetic Engineering
- Hepatocellular Carcinoma Treatment and Prognosis
- RNA modifications and cancer
- Pancreatic and Hepatic Oncology Research
- BRCA gene mutations in cancer
- Genomics and Phylogenetic Studies
- Cancer-related gene regulation
- Genomic variations and chromosomal abnormalities
- Effects of Radiation Exposure
Genome Research Foundation
2022-2024
Korea Advanced Institute of Science and Technology
2020-2024
Genome Insight (South Korea)
2022-2023
Throughout an individual's lifetime, genomic alterations accumulate in somatic cells
The role of the serine/glycine metabolic pathway (SGP) has recently been demonstrated in tumors; however, pathological relevance SGP thyroid cancer remains unexplored. Here, we perform metabolomic profiling 17 tumor-normal pairs; bulk transcriptomics 263 normal thyroid, 348 papillary, and 21 undifferentiated samples; single-cell transcriptomes from 15 cases, showing impact mitochondrial one-carbon metabolism tumors. High expression serine hydroxymethyltransferase-2 (SHMT2)...
The comprehensive genomic impact of ionizing radiation (IR), a carcinogen, on healthy somatic cells remains unclear. Using large-scale whole-genome sequencing (WGS) clones expanded from irradiated murine and human single cells, we revealed that IR induces characteristic spectrum short insertions or deletions (indels) structural variations (SVs), including balanced inversions, translocations, composite SVs (deletion-insertion, deletion-inversion, deletion-translocation composites), complex...
This study aimed to implement genome sequencing using an automated pipeline for critically ill pediatric patients within a real-world healthcare system. Twenty under 36 months of age, admitted the NICU/PICU or suspected having rapidly progressive genetic disorders, were enrolled. Trio-based was performed optimized processing pipeline, which automatically mapping, variant calling, annotation, and in silico pathogenicity assessment. Among 20 enrolled patients, 11 (55%) from NICU, 16 (80%)...
Abstract Genomic alterations in tumors play a pivotal role determining their clinical trajectory and responsiveness to treatment. Targeted panel sequencing (TPS) has served as key tool over the past decade, but advancements costs bioinformatics have now made whole-genome (WGS) feasible single-assay approach for almost all cancer genomes settings. This paper reports on findings of prospective, single-center study exploring real-world utility WGS (tumor matched normal tissues) two primary...
Abstract Genomic alterations in tumors play a pivotal role determining their clinical trajectory and responsiveness to treatment. While targeted panel sequencing ( TPS ) has been key tool over the past decade, advancements costs bioinformatics have now made whole-genome WGS feasible single-assay approach for almost all cancer genomes settings. This paper reports on findings of prospective, single-center study exploring real-world utility (tumor matched normal tissues) with two primary...
554 Background: Homologous recombination deficiency (HRD) in breast cancer is an actionable target, with treatment efficacy potentially linked to timely detection. Notably, BRCA1 and BRCA2 are key genes implicated HRD, their pathogenic germline mutations crucial criteria for the use of poly (ADP-ribose) polymerase inhibitors (PARPi). Although BRCA1/2 detectable only a small fraction (1-5%) cancers, recent whole-genome sequencing (WGS) studies have revealed that up 22% cancers also exhibit...
ABSTRACT Cancer poses a significant global health challenge, with increasing incidence rates demanding precise genomic testing for individualized treatment strategies. Targeted-panel sequencing (TPS) has improved personalized oncology but often lacks comprehensive coverage of crucial cancer alterations. Whole-genome (WGS) addresses this gap, offering extensive testing. This study demonstrates the potential medical application WGS. Methods evaluates power target-enhanced WGS (TE-WGS),...
Abstract Whole-genome sequencing (WGS) of human tumors and normal cells exposed to various carcinogens has revealed distinct mutational patterns that provide deep insights into the DNA damage repair processes. Although ionizing radiation (IR) is conventionally known as a strong carcinogen, its genome-wide impacts have not been comprehensively investigated at single-nucleotide level. Here, we explored landscape single-cells after exposure levels IR. On average, 1 Gy IR generated ∼16 events...
Abstract The roles of the serine/glycine metabolic pathway (SGP) have recently been evident in certain types tumor physiology; however, pathological relevance SGP undifferentiated thyroid cancer remains unexplored. Herein, we employed a comparative transcriptome analysis bulk RNA sequencing coupled with single-cell sequencing, showing that high expression SHMT2 and MTHFD2 is tightly associated low differentiation score (TDS) poor clinical features cancer. In addition, unique reprogramming...
Abstract Formalin-Fixed Paraffin-Embedded (FFPE) specimens, widely utilized in clinical cancer diagnostics, present significant challenges by introducing artifacts into genomic data. This study aimed to profile these FFPE-induced alterations, with a particular focus on single-nucleotide variants (SNVs), small insertions and deletions (indels), copy-number variations (CNVs), develop computational methods for filtering out such artifacts. Our primary was twofold: first, comprehensively...
Cancer poses a significant global health challenge, demanding precise genomic testing for individualized treatment strategies. Targeted-panel sequencing (TPS) has improved personalized oncology but often lacks comprehensive coverage of crucial cancer alterations. Whole-genome (WGS) addresses this gap, offering extensive testing. This study demonstrates the medical potential WGS.
<title>Abstract</title> Recent advancements in genomic technologies have become critical tools for deciphering the genetic complexities of cancer tissues, enabling precision medicine strategies aimed at improving patient clinical outcomes. Here we performed a comprehensive analysis clinically annotated whole genome and transcriptome sequences from 1,364 breast cases. Our investigation provides most detailed landscapes to date, which allowed us comprehensively correlate changes with...
Abstract Cancer genomes frequently carry APOBEC (apolipoprotein B mRNA editing catalytic polypeptide-like)-associated DNA mutations, suggesting enzymes as innate mutagens during cancer initiation and/or evolution. However, the pure mutagenic impacts of specific among this family that are responsible for APOBEC-associated mutagenesis remain unclear, particularly comparative activities APOBEC3A and APOBEC3B . Here, we investigated contributions these through whole-genome sequencing human...
Summary The trillions of cells that constitute the human body are developed from a fertilized egg through embryogenesis. However, cellular dynamics and developmental outcomes embryonic in humans remain to be largely unknown due technical ethical challenges. Here, we explored whole-genomes 334 single-cell expanded clones targeted deep-sequences 379 bulk tissues obtained various anatomical locations seven individuals. Using discovered 1,688,652 somatic mutations as an intrinsic barcode,...
Summary Over the course of an individual’s lifetime, genomic alterations accumulate in somatic cells. However, mutational landscape by retrotranspositions long interspersed nuclear element-1 ( L1 ), a widespread mobile element human genome, is poorly understood normal Here, we explored whole-genome sequences 892 single-cell clones established from various tissues collected 28 individuals. Remarkably, 88% colorectal epithelial cells acquired soL1Rs carrying ∼3 events per cell on average with...
Abstract Breast cancers (BCs) with defects in homologous recombination repair (HRR) pathway depend on the Poly (ADP-ribose) polymerase enzymes (PARP) for their survival and thus are sensitive to PARP inhibitors (PARPi). To screen out BCs deficiency (HRD), germline mutations BRCA genes have been tested, which constitute approximately 5% of unselected BC patients. However, a substantial proportion show HRD phenotypes despite absence inactivating germline. Herein, we apply whole-genome...
Abstract Medullary thyroid carcinoma (MTC) is a rare malignancy derived from the parafollicular C cells of gland. It features relatively aggressive biologic behavior among cancers, but its genomic landscape has not yet been fully explored. Here, we conducted multi-omics data (whole genome sequencing (WGS), and bulk (bulk RNA-seq) or single nucleus RNA (snRNA-seq)) on MTC, found genetic characteristics MTC new gene signature predicting aggressiveness tumors. WGS was performed for 35 pairs...
Abstract Liver cancer is a leading cause of death worldwide where somatic mutation plays key role in tumorigenesis. As such, many recent researches have been conducted using DNA sequencing methods to study mutations liver cancer, such as whole-exome (WES), panel sequencing, and whole-genome (WGS). However, our understanding genomic landscape tumorigenesis has limited by low number quality samples from diverse clinical contexts. Here, we explore comprehensive throughout its large-scale...
Abstract Breast cancers (BCs) with defects in homologous recombination repair (HRR) pathway depend on the Poly (ADP-ribose) polymerase enzymes (PARP) for their survival and thus are sensitive to PARP inhibitors (PARPi). To screen out BCs deficiency (HRD), germline mutations BRCA genes have been tested, which constitute approximately 5% of unselected BC patients. However, a substantial proportion show HRD phenotypes despite absence inactivating germline. Herein, we apply whole-genome...
Abstract Lung adenocarcinoma (LADC) is the most common type of lung cancer and a leading cause death worldwide. Typical oncogenes that drive LADCs when mutated (referred to as canonical drivers) include EGFR (30-60%), KRAS (10-30%), fusion (~10%) involving ALK, RET, ROS1. However, approximately 30% adenocarcinomas lack drivers, implying unseen kinds genomic alterations. Here, we explore alterations beyond scope drivers in non-canonical using large-scale whole-genome sequencing (WGS) LADCs....
e15173 Background: Due to the dramatic decrease in cost of genome sequencing, we are entering era whole sequencing (WGS) at $100. Tumor mutational burden (TMB) and signatures have been introduced as potential prognostic/predictive cancer biomarkers mostly assessed by targeted gene panels. However, they truly genome-wide events thus more accurately estimated data. Methods: We analyzed WGS data produced Genome Insight Inc. that encompass > 1,300 breast, lung, hepatocellular carcinoma...
568 Background: Recently, genomic features have proven effective at gene-agnostic detection of homologous recombination deficiency (HRD). However, it remains to be explored what extent we can exploit genome analysis assess HRD status. Here, show that a machine learning (ML) classifier based on mutational signatures enables robust and subtyping outperforms current state-of-the-art classifier. Methods: We whole-genome-sequenced (WGS) ~700 breast cancers identified pathogenic variants in...