A5044008222- Chronic Lymphocytic Leukemia Research
- Acute Myeloid Leukemia Research
- Epigenetics and DNA Methylation
- Lymphoma Diagnosis and Treatment
- Immune Cell Function and Interaction
- RNA modifications and cancer
- Acute Lymphoblastic Leukemia research
- Immunodeficiency and Autoimmune Disorders
- Cancer-related molecular mechanisms research
- Myeloproliferative Neoplasms: Diagnosis and Treatment
- Cancer Genomics and Diagnostics
- Cancer-related gene regulation
- Viral-associated cancers and disorders
- Histone Deacetylase Inhibitors Research
- Protein Degradation and Inhibitors
- Chronic Myeloid Leukemia Treatments
- Glycosylation and Glycoproteins Research
- Pancreatic and Hepatic Oncology Research
- Genomics and Chromatin Dynamics
- MicroRNA in disease regulation
- Genetics and Neurodevelopmental Disorders
- Multiple Myeloma Research and Treatments
- Pancreatic function and diabetes
- Genetic Syndromes and Imprinting
- Diabetes Treatment and Management
The Ohio State University
2016-2025
The Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital and Richard J. Solove Research Institute
2017-2024
The Ohio State University Wexner Medical Center
2021-2024
Sylvester Comprehensive Cancer Center
2023
Heidelberg University
2010-2022
German Cancer Research Center
2010-2022
University of Duisburg-Essen
2021
Ohio Supercomputer Center
2020-2021
Epigenomics (Germany)
2010-2019
Universität Ulm
2012-2013
Despite much evidence on epigenetic abnormalities in cancer, it is currently unclear to what extent alterations can be associated with tumors' clonal genetic origins. Here, we show that the prostate intratumor heterogeneity DNA methylation and copy-number patterns explained by a unified evolutionary process. By assaying multiple topographically distinct tumor sites, premalignant lesions, lymph node metastases within five cases of demonstrate both consistently reflect life history tumors....
Abstract Recently, the European LeukemiaNet (ELN) revised its genetic-risk classification of acute myeloid leukemia (AML). We categorized 1637 adults with AML treated cytarabine/anthracycline regimens according to 2022 and 2017 ELN classifications. Compared classification, favorable group decreased from 40% 35% adverse increased 37% 41% patients. The groups seemed accurately reflect treatment outcomes in all patients aged <60 years, but ≥60 relapse rates, disease-free (DFS) overall (OS)...
The development of germ cells is a highly ordered process that begins during fetal growth and completed in the adult. Epigenetic modifications occur are important for cell function post-fertilization embryonic development. We have previously shown male adult mouse distinct epigenetic state, as revealed by unique genome-wide pattern DNA methylation. Although it known these patterns begin to be established life, not what extent methylation modified spermatogenesis. used restriction landmark...
Non-coding RNAs are much more common than previously thought. However, for the vast majority of non-coding RNAs, cellular function remains enigmatic. The two long RNA (lncRNA) genes DLEU1 and DLEU2 map to a critical region at chromosomal band 13q14.3 that is recurrently deleted in solid tumors hematopoietic malignancies like chronic lymphocytic leukemia (CLL). While no point mutations have been found protein coding candidate 13q14.3, they deregulated malignant cells, suggesting an epigenetic...
Although clonal selection by genetic driver aberrations in cancer is well documented, the ability of epigenetic alterations to promote tumor evolution undefined. We used 450k arrays and next-generation sequencing evaluate intratumor heterogeneity DNA methylation chronic lymphocytic leukemia (CLL). CLL cases exhibit vast interpatient differences heterogeneity, with genetically maintaining low up 10% total CpGs a monoallelically methylated state. Increasing correlates advanced subclonal...
Increased ZAP-70 expression predicts poor prognosis in chronic lymphocytic leukemia (CLL). Current methods for accurately measuring are problematic, preventing widespread application of these tests clinical decision making. We therefore used comprehensive DNA methylation profiling the regulatory region to identify sites important transcriptional control.High-resolution quantitative analysis entire gene regions was conducted on 247 samples from patients with CLL four independent...
As new generations of targeted therapies emerge and tumor genome sequencing discovers increasingly comprehensive mutation repertoires, the functional relationships mutations to phenotypes remain largely unknown. Here, we measured ex vivo sensitivity 246 blood cancers 63 drugs alongside genome, transcriptome, DNA methylome analysis understand determinants drug response. We assembled a primary cancer cell encyclopedia data set that revealed disease-specific sensitivities for each cancer....
There is a concern that increased paternal age may be associated with altered fertility and an incidence of birth defects in man. In previous studies aged male rats, we have found abnormalities the embryos sired by older males. Aging mammals alterations content patterns DNA methylation somatic cells; however, little known regard to germ cells. A systematic search for global gene-specific cells liver rats was done. Restriction landmark genomic scanning, method used determine specific CpG...
In the mammalian lifecycle, two periods of genome-wide epigenetic reprogramming are in early embryo, when somatic patterns set, and during germ cell development. Although some differences between reprogrammed states cells have been reported, overall genomic methylation considered to be similar. Using restriction landmark scanning examine ≈2,600 loci distributed randomly throughout genome, we find that status testicular DNA is highly distinct, displaying eightfold number hypomethylated...
Histone methyltransferases (HMTs) are important epigenetic regulators of gene transcription and disrupted at the genomic level in a spectrum human tumours including haematological malignancies. Using high-resolution single nucleotide polymorphism (SNP) arrays, we identified recurrent deletions SETD2 locus 3% (8/261) chronic lymphocytic leukaemia (CLL) patients. Further validation two independent cohorts showed that were associated with loss TP53, complexity chromothripsis. With...
Clinical outcome of patients with acute myeloid leukemia (AML) is associated cytogenetic and molecular factors patient demographics (e.g., age race). We compared survival 25,523 non-Hispanic Black White adults AML using Surveillance Epidemiology End Results (SEER) Program data performed mutational profiling 1,339 treated on frontline Alliance for Trials in Oncology (Alliance) protocols. had shorter than patients, both SEER the setting clinical trials. The disparity was especially pronounced...
Abstract Cancer development is an evolutionary genomic process with parallels to Darwinian selection. It requires acquisition of multiple somatic mutations that collectively cause a malignant phenotype and continuous clonal evolution often linked tumor progression. Here, we show the structure in 15 myelofibrosis (MF) patients while receiving treatment JAK inhibitors (mean follow-up 3.9 years). Whole-exome sequencing at time points reveal copy number aberrations over time. While inhibition...
DNA methylation in mammals has been shown to play many important roles diverse biological phenomena. Several methods have developed for the measurement of region-specific levels methylation. We sought a technique that could be used quantitatively evaluate multiple independent loci several tissues quick and cost-effective manner. Recently, few quantitative techniques by employing use real-time PCR, though they require additional step sodium bisulfite conversion. Here we involves digestion...