Jake June-Koo Lee
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View article: Integrated histopathologic modeling of detailed tumor subtypes and actionable biomarkers
Integrated histopathologic modeling of detailed tumor subtypes and actionable biomarkers Open
Accurate cancer subtyping with accompanying molecular characterization is critical for precision oncology. While machine learning approaches have been applied to both digital pathology and cancer genomics, previous work has been limited in…
View article: Complementary modes of resistance to<i>EGFR</i>TKI in lung adenocarcinoma through MAPK activation and cellular plasticity
Complementary modes of resistance to<i>EGFR</i>TKI in lung adenocarcinoma through MAPK activation and cellular plasticity Open
EGFR -mutant lung adenocarcinoma (LUAD) represents 20% of all non-small cell lung carcinomas, with most patients presenting with incurable metastatic disease. Treatment with mutant-selective EGFR tyrosine kinase inhibitors (TKIs) results i…
View article: Figure 3 from Chromothripsis-Mediated Small Cell Lung Carcinoma
Figure 3 from Chromothripsis-Mediated Small Cell Lung Carcinoma Open
Chromothripsis and corresponding cancer gene amplifications and losses. A, Representative Circos plots of SVs and CNAs across the genome by WGS. Outer band shows an ideogram of chromosome positions and cytogenetic bands. Second band depict…
View article: Data from Chromothripsis-Mediated Small Cell Lung Carcinoma
Data from Chromothripsis-Mediated Small Cell Lung Carcinoma Open
Small cell lung carcinoma (SCLC) is a highly aggressive malignancy that is typically associated with tobacco exposure and inactivation of RB1 and TP53 genes. Here, we performed detailed clinicopathologic, genomic, and transcriptomic profil…
View article: Figure 1 from Chromothripsis-Mediated Small Cell Lung Carcinoma
Figure 1 from Chromothripsis-Mediated Small Cell Lung Carcinoma Open
Cohort selection and clinicopathologic characteristics. A, Schematic diagram of RB1 and TP53 inactivation (outer doughnut) and smoking status (inner doughnut) in a cohort of 600 consecutive SCLC that underwent tNGS by MSK-IMPACT. RB1 and T…
View article: Supplementary Tables S1-S13 from Chromothripsis-Mediated Small Cell Lung Carcinoma
Supplementary Tables S1-S13 from Chromothripsis-Mediated Small Cell Lung Carcinoma Open
Supplementary Table S1. Integrated genomic and immunohistochemical results for TP53 and RB1 in aSCLC Supplementary Table S2. Demographic, clinicopathologic and immunohistochemical characteristics: Per patient data Supplementary Table S3. S…
View article: Figure 7 from Chromothripsis-Mediated Small Cell Lung Carcinoma
Figure 7 from Chromothripsis-Mediated Small Cell Lung Carcinoma Open
Outcome and treatment responses. A, Kaplan–Meier analysis of the disease-specific overall survival assessed from the time of diagnosis. B, Pie chart summarizing radiologic treatment response to platinum-based chemotherapy received in any l…
View article: Figure 6 from Chromothripsis-Mediated Small Cell Lung Carcinoma
Figure 6 from Chromothripsis-Mediated Small Cell Lung Carcinoma Open
Comparison of aSCLC vs. RB1−/TP53− nsSCLC: the dual model of SCLC pathogenesis in never-smokers. A, Lines of evidence for a histogenetic relationship between aSCLC and carcinoids or their progenitors, including histologic evidence of carci…
View article: Supplementary Figures S1-S13 from Chromothripsis-Mediated Small Cell Lung Carcinoma
Supplementary Figures S1-S13 from Chromothripsis-Mediated Small Cell Lung Carcinoma Open
Supplementary Figure S1. Detailed morphologic and immunohistochemical findings: Case A01. Supplementary Figure S2. Detailed morphologic and immunohistochemical findings: Case A08. Supplementary Figure S3. Detailed morphologic and immunohis…
View article: Figure 5 from Chromothripsis-Mediated Small Cell Lung Carcinoma
Figure 5 from Chromothripsis-Mediated Small Cell Lung Carcinoma Open
Multisample analysis from all temporally or spatially distinct samples obtained for each patient. A, Conservation of chromothripsis and corresponding amplifications across all samples with available data from individual patients. ^ indicat…
View article: Figure 2 from Chromothripsis-Mediated Small Cell Lung Carcinoma
Figure 2 from Chromothripsis-Mediated Small Cell Lung Carcinoma Open
Mutation and CNA landscape of aSCLC. A, Mutations and CNAs in aSCLC in comparison to the control groups of sSCLC (n = 206) and pulmonary carcinoids (n = 157) analyzed by MSK-IMPACT. OncoPrint summarizing assays performed and overall genomi…
View article: Figure 4 from Chromothripsis-Mediated Small Cell Lung Carcinoma
Figure 4 from Chromothripsis-Mediated Small Cell Lung Carcinoma Open
Chromosomal architecture of chromothripsis and amplifications. A, Integrated SV and CNA analysis in two representative cases confirming the hallmark features of chromothripsis and suggesting formation of ecDNA and micronucleation as a mech…
View article: Chromothripsis-Mediated Small Cell Lung Carcinoma
Chromothripsis-Mediated Small Cell Lung Carcinoma Open
Small cell lung carcinoma (SCLC) is a highly aggressive malignancy that is typically associated with tobacco exposure and inactivation of RB1 and TP53 genes. Here, we performed detailed clinicopathologic, genomic, and transcriptomic profil…
View article: Tracking clonal evolution of drug resistance in ovarian cancer patients by exploiting structural variants in cfDNA
Tracking clonal evolution of drug resistance in ovarian cancer patients by exploiting structural variants in cfDNA Open
Drug resistance is the major cause of therapeutic failure in high-grade serous ovarian cancer (HGSOC). Yet, the mechanisms by which tumors evolve to drug resistant states remains largely unknown. To address this, we aimed to exploit clone-…
View article: Predicting response to immune checkpoint blockade therapy among mismatch repair-deficient patients using mutational signatures
Predicting response to immune checkpoint blockade therapy among mismatch repair-deficient patients using mutational signatures Open
Despite the overall efficacy of immune checkpoint blockade (ICB) for mismatch repair deficiency (MMRD) across tumor types, a sizable fraction of patients with MMRD still do not respond to ICB. We performed mutational signature analysis of …
View article: ERα-associated translocations underlie oncogene amplifications in breast cancer
ERα-associated translocations underlie oncogene amplifications in breast cancer Open
Focal copy-number amplification is an oncogenic event. Although recent studies have revealed the complex structure 1–3 and the evolutionary trajectories 4 of oncogene amplicons, their origin remains poorly understood. Here we show that foc…
View article: Author Correction: Comprehensive analysis of chromothripsis in 2,658 human cancers using whole-genome sequencing
Author Correction: Comprehensive analysis of chromothripsis in 2,658 human cancers using whole-genome sequencing Open
Correction to: Nature Genetics, published online 05 February 2020. In the published version of this paper, the members of the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium were listed in the Supplementary Information; however, th…
View article: Author Correction: Pan-cancer analysis of whole genomes identifies driver rearrangements promoted by LINE-1 retrotransposition
Author Correction: Pan-cancer analysis of whole genomes identifies driver rearrangements promoted by LINE-1 retrotransposition Open
Correction to: Nature Genetics, published online 05 February 2020. In the published version of this paper, the members of the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium were listed in the Supplementary Information; however, th…
View article: Whole-genome characterization of lung adenocarcinomas lacking alterations in the RTK/RAS/RAF pathway
Whole-genome characterization of lung adenocarcinomas lacking alterations in the RTK/RAS/RAF pathway Open
RTK/RAS/RAF pathway alterations (RPAs) are a hallmark of lung adenocarcinoma (LUAD). In this study, we use whole-genome sequencing (WGS) of 85 cases found to be RPA(-) by previous studies from The Cancer Genome Atlas (TCGA) to characterize…
View article: A fusion of CD63–BCAR4 identified in lung adenocarcinoma promotes tumorigenicity and metastasis
A fusion of CD63–BCAR4 identified in lung adenocarcinoma promotes tumorigenicity and metastasis Open
Background Recently, fusion variants of the breast cancer anti-oestrogen-resistance 4 (BCAR4) gene were recurrently discovered in lung adenocarcinoma from the genome-wide studies. However, the functional characterisation of BCAR4 fusion ha…
View article: Orphan nuclear receptor COUP-TFII drives the myofibroblast metabolic shift leading to fibrosis
Orphan nuclear receptor COUP-TFII drives the myofibroblast metabolic shift leading to fibrosis Open
Recent studies demonstrated that metabolic disturbance, such as augmented glycolysis, contributes to fibrosis. The molecular regulation of this metabolic perturbation in fibrosis, however, has been elusive. COUP-TFII (also known as NR2F2) …