Michael D. McLellan
A5089826284- Cancer Genomics and Diagnostics
- Acute Myeloid Leukemia Research
- Immunotherapy and Immune Responses
- Epigenetics and DNA Methylation
- RNA modifications and cancer
- Genetic factors in colorectal cancer
- Bioinformatics and Genomic Networks
- Genomics and Phylogenetic Studies
- Genomics and Rare Diseases
- Cancer Immunotherapy and Biomarkers
- Lung Cancer Treatments and Mutations
- Cancer-related molecular mechanisms research
- Genomics and Chromatin Dynamics
- RNA Research and Splicing
- Genomic variations and chromosomal abnormalities
- Protein Degradation and Inhibitors
- Molecular Biology Techniques and Applications
- Monoclonal and Polyclonal Antibodies Research
- Cancer-related Molecular Pathways
- Genetics, Bioinformatics, and Biomedical Research
- Gene expression and cancer classification
- Myeloproliferative Neoplasms: Diagnosis and Treatment
- Ferroptosis and cancer prognosis
- DNA Repair Mechanisms
- Evolution and Genetic Dynamics
James S. McDonnell Foundation
2015-2024
Washington University in St. Louis
2012-2023
Alvin J. Siteman Cancer Center
2020-2023
National Human Genome Research Institute
2021
Henry Ford Health System
2008-2021
George Washington University
2018
Research Network (United States)
2017
University of Iowa
2017
Novartis (United States)
2015
Seattle University
2014
We analysed primary breast cancers by genomic DNA copy number arrays, methylation, exome sequencing, messenger RNA microRNA sequencing and reverse-phase protein arrays. Our ability to integrate information across platforms provided key insights into previously defined gene expression subtypes demonstrated the existence of four main cancer classes when combining data from five platforms, each which shows significant molecular heterogeneity. Somatic mutations in only three genes (TP53, PIK3CA...
Gastric cancer is a leading cause of deaths, but analysis its molecular and clinical characteristics has been complicated by histological aetiological heterogeneity. Here we describe comprehensive evaluation 295 primary gastric adenocarcinomas as part The Cancer Genome Atlas (TCGA) project. We propose classification dividing into four subtypes: tumours positive for Epstein–Barr virus, which display recurrent PIK3CA mutations, extreme DNA hypermethylation, amplification JAK2, CD274 (also...
We performed an integrated genomic, transcriptomic and proteomic characterization of 373 endometrial carcinomas using array- sequencing-based technologies. Uterine serous tumours ∼25% high-grade endometrioid had extensive copy number alterations, few DNA methylation changes, low oestrogen receptor/progesterone receptor levels, frequent TP53 mutations. Most alterations or mutations, but mutations in PTEN, CTNNB1, PIK3CA, ARID1A KRAS novel the SWI/SNF chromatin remodelling complex gene ARID5B....
Many mutations that contribute to the pathogenesis of acute myeloid leukemia (AML) are undefined. The relationships between patterns and epigenetic phenotypes not yet clear. We analyzed genomes 200 clinically annotated adult cases de novo AML, using either whole-genome sequencing (50 cases) or whole-exome (150 cases), along with RNA microRNA DNA-methylation analysis. AML have fewer than most other cancers, an average only 13 found in genes. Of these, 5 genes recurrently mutated AML. A total...
Cancer is a disease driven by genetic variation and mutation. Exome sequencing can be utilized for discovering these variants mutations across hundreds of tumors. Here we present an analysis tool, VarScan 2, the detection somatic copy number alterations (CNAs) in exome data from tumor-normal pairs. Unlike most current approaches, our algorithm reads both samples simultaneously; heuristic statistical detects sequence classifies them status (germline, somatic, or LOH); while comparison...
The Cancer Genome Atlas (TCGA) has used the latest sequencing and analysis methods to identify somatic variants across thousands of tumours. Here we present data analytical results for point mutations small insertions/deletions from 3,281 tumours 12 tumour types as part TCGA Pan-Cancer effort. We illustrate distributions mutation frequencies, contexts types, establish their links tissues origin, environmental/carcinogen influences, DNA repair defects. Using integrated sets, identified 127...
The full complement of DNA mutations that are responsible for the pathogenesis acute myeloid leukemia (AML) is not yet known.We used massively parallel sequencing to obtain a very high level coverage (approximately 98%) primary, cytogenetically normal, de novo genome AML with minimal maturation (AML-M1) and matched normal skin genome.We identified 12 acquired (somatic) within coding sequences genes 52 somatic point in conserved or regulatory portions genome. All appeared be heterozygous...
The sequencing of AML genomes eight patients before and after relapse reveals two major patterns clonal evolution, with chemotherapy appearing to have a role in both patterns. Many acute myeloid leukaemia (AML) achieve remission, but it is often short-lived the returned disease usually refractory therapy. Genome tumour cell evolution. founding clone survives all patients, and, one pattern, acquires new mutations expands at relapse. In other, subclone surviving from original then mutations....
The genetic alterations responsible for an adverse outcome in most patients with acute myeloid leukemia (AML) are unknown.Using massively parallel DNA sequencing, we identified a somatic mutation DNMT3A, encoding methyltransferase, the genome of cells from patient AML normal karyotype. We sequenced exons DNMT3A 280 additional de novo to define recurring mutations.A total 62 281 (22.1%) had mutations that were predicted affect translation. 18 different missense mutations, common which was...
Acute myeloid leukaemia is a highly malignant haematopoietic tumour that affects about 13,000 adults in the United States each year. The treatment of this disease has changed little past two decades, because most genetic events initiate remain undiscovered. Whole-genome sequencing now possible at reasonable cost and timeframe to use approach for unbiased discovery tumour-specific somatic mutations alter protein-coding genes. Here we present results obtained from typical acute genome, its...
Abstract Summary: Massively parallel sequencing technologies hold incredible promise for the study of DNA sequence variation, particularly identification variants affecting human disease. The unprecedented throughput and relatively short read lengths Roche/454, Illumina/Solexa, other platforms have spurred development a new generation alignment algorithms. Yet detection based on alignments remains challenging, most currently available tools are limited to single platform or aligner type. We...
To correlate the variable clinical features of oestrogen-receptor-positive breast cancer with somatic alterations, we studied pretreatment tumour biopsies accrued from patients in two studies neoadjuvant aromatase inhibitor therapy by massively parallel sequencing and analysis. Eighteen significantly mutated genes were identified, including five (RUNX1, CBFB, MYH9, MLL3 SF3B1) previously linked to haematopoietic disorders. Mutant MAP3K1 was associated luminal A status, low-grade histology...
The Cancer Genome Atlas (TCGA) cancer genomics dataset includes over 10,000 tumor-normal exome pairs across 33 different types, in total >400 TB of raw data files requiring analysis. Here we describe the Multi-Center Mutation Calling Multiple Cancers project, our effort to generate a comprehensive encyclopedia somatic mutation calls for TCGA enable robust cross-tumor-type analyses. Our approach accounts variance and batch effects introduced by rapid advancement DNA extraction,...
The myelodysplastic syndromes are a group of hematologic disorders that often evolve into secondary acute myeloid leukemia (AML). genetic changes underlie progression from the to AML not well understood.