Joshua Armenia
A5021762206- Cancer Genomics and Diagnostics
- Prostate Cancer Treatment and Research
- PARP inhibition in cancer therapy
- RNA modifications and cancer
- Science, Research, and Medicine
- Cancer, Lipids, and Metabolism
- CRISPR and Genetic Engineering
- Metal-Catalyzed Oxygenation Mechanisms
- Health Systems, Economic Evaluations, Quality of Life
- Cancer Immunotherapy and Biomarkers
- Medical Imaging and Pathology Studies
- DNA Repair Mechanisms
- Occupational and environmental lung diseases
- Ferroptosis and cancer prognosis
- Genetic factors in colorectal cancer
- Cancer-related molecular mechanisms research
- MicroRNA in disease regulation
- Salivary Gland Tumors Diagnosis and Treatment
- Epigenetics and DNA Methylation
- Cancer-related Molecular Pathways
- Cancer-related gene regulation
- Molecular Biology Techniques and Applications
- Prostate Cancer Diagnosis and Treatment
- Genomics and Phylogenetic Studies
- Genomics and Rare Diseases
Memorial Sloan Kettering Cancer Center
2016-2023
Molecular Oncology (United States)
2017-2023
AstraZeneca (United Kingdom)
2019-2023
AstraZeneca (Brazil)
2022
Kettering University
2016-2019
Washington University in St. Louis
2018
University of California, Santa Cruz
2018
Bayer (United States)
2018
James S. McDonnell Foundation
2018
Research Network (United States)
2018
Abstract Somatic mutations in cancer genomes are caused by multiple mutational processes, each of which generates a characteristic signature 1 . Here, as part the Pan-Cancer Analysis Whole Genomes (PCAWG) Consortium 2 International Cancer Genome (ICGC) and The Atlas (TCGA), we characterized signatures using 84,729,690 somatic from 4,645 whole-genome 19,184 exome sequences that encompass most types cancer. We identified 49 single-base-substitution, 11 doublet-base-substitution, 4...
For a decade, The Cancer Genome Atlas (TCGA) program collected clinicopathologic annotation data along with multi-platform molecular profiles of more than 11,000 human tumors across 33 different cancer types. TCGA clinical contain key features representing the democratized nature collection process. To ensure proper use this large dataset associated genomic features, we developed standardized named Pan-Cancer Clinical Data Resource (TCGA-CDR), which includes four major outcome endpoints. In...
Highlights•Alteration map of 10 signaling pathways across 9,125 samples from 33 cancer types•Reusable, curated pathway templates that include a catalogue driver genes•57% tumors have at least one potentially actionable alteration in these pathways•Co-occurrence alterations suggests combination therapy opportunitiesSummaryGenetic control cell-cycle progression, apoptosis, and cell growth are common hallmarks cancer, but the extent, mechanisms, co-occurrence differ between individual tumor...
Abstract Cancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation this variation at whole-genome scale 1–3 . Here we report integrative analysis 2,658 whole-cancer genomes their matching normal tissues across 38 tumour types from Pan-Cancer Analysis Whole Genomes (PCAWG) Consortium International Genome (ICGC) The Atlas (TCGA). We describe generation PCAWG resource, facilitated international data sharing using compute clouds. On...
We conducted comprehensive integrative molecular analyses of the complete set tumors in The Cancer Genome Atlas (TCGA), consisting approximately 10,000 specimens and representing 33 types cancer. performed clustering using data on chromosome-arm-level aneuploidy, DNA hypermethylation, mRNA, miRNA expression levels reverse-phase protein arrays, which all, except for revealed primarily organized by histology, tissue type, or anatomic origin. influence cell type was evident...
Cancer progression involves the gradual loss of a differentiated phenotype and acquisition progenitor stem-cell-like features. Here, we provide novel stemness indices for assessing degree oncogenic dedifferentiation. We used an innovative one-class logistic regression (OCLR) machine-learning algorithm to extract transcriptomic epigenetic feature sets derived from non-transformed pluripotent stem cells their progeny. Using OCLR, were able identify previously undiscovered biological mechanisms...
Heterogeneity in the genomic landscape of metastatic prostate cancer has become apparent through several comprehensive profiling efforts, but little is known about impact this heterogeneity on clinical outcome. Here, we report and transcriptomic analysis 429 patients with castration-resistant (mCRPC) linked longitudinal outcomes, integrating findings from whole-exome, transcriptome, histologic analysis. For 128 treated a first-line next-generation androgen receptor signaling inhibitor (ARSI;...
Aneuploidy, whole chromosome or arm imbalance, is a near-universal characteristic of human cancers. In 10,522 cancer genomes from The Cancer Genome Atlas, aneuploidy was correlated with TP53 mutation, somatic mutation rate, and expression proliferation genes. Aneuploidy anti-correlated immune signaling genes, due to decreased leukocyte infiltrates in high-aneuploidy samples. Chromosome arm-level alterations show cancer-specific patterns, including loss 3p squamous We applied genome...
Beyond sample curation and basic pathologic characterization, the digitized H&E-stained images of TCGA samples remain underutilized. To highlight this resource, we present mappings tumor-infiltrating lymphocytes (TILs) based on H&E from 13 tumor types. These TIL maps are derived through computational staining using a convolutional neural network trained to classify patches images. Affinity propagation revealed local spatial structure in patterns correlation with overall survival. map...
Our comprehensive analysis of alternative splicing across 32 The Cancer Genome Atlas cancer types from 8,705 patients detects events and tumor variants by reanalyzing RNA whole-exome sequencing data. Tumors have up to 30% more than normal samples. Association somatic with confirmed known trans associations in SF3B1 U2AF1 identified additional trans-acting (e.g., TADA1, PPP2R1A). Many tumors thousands not detectable samples; on average, we ≈930 exon-exon junctions ("neojunctions") typically...
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 anti-programmed cell death protein 1 (PD-1) antibody pembrolizumab is approved by the US Food and Drug Administration for treatment of microsatellite instability-high (MSI-H) or mismatch repair-deficient (dMMR) solid tumors, but prevalence MSI-H/dMMR prostate cancer clinical utility immune checkpoint blockade in this disease subset are unknown.To define benefit anti-PD-1/programmed ligand (PD-L1) therapy molecularly defined population.In case series, 1551 tumors from 1346 patients with...
Gene fusions represent an important class of somatic alterations in cancer. We systematically investigated 9,624 tumors across 33 cancer types using multiple fusion calling tools. identified a total 25,664 fusions, with 63% validation rate. Integration gene expression, copy number, and annotation data revealed that involving oncogenes tend to exhibit increased whereas tumor suppressors have the opposite effect. For kinases, we found 1,275 intact kinase domain, proportion which varied...
Abstract Malignant pleural mesothelioma (MPM) is a highly lethal cancer of the lining chest cavity. To expand our understanding MPM, we conducted comprehensive integrated genomic study, including most detailed analysis BAP1 alterations to date. We identified histology-independent molecular prognostic subsets, and defined novel subtype with TP53 SETDB1 mutations extensive loss heterozygosity. also report strong expression immune-checkpoint gene VISTA in epithelioid strikingly higher than...
We analyzed 921 adenocarcinomas of the esophagus, stomach, colon, and rectum to examine shared distinguishing molecular characteristics gastrointestinal tract (GIACs). Hypermutated tumors were distinct regardless cancer type comprised those enriched for insertions/deletions, representing microsatellite instability cases with epigenetic silencing MLH1 in context CpG island methylator phenotype, plus elevated single-nucleotide variants associated mutations POLE. Tumors chromosomal diverse,...
Abstract Purpose: Prior molecular profiling of hepatocellular carcinoma (HCC) has identified actionable findings that may have a role in guiding therapeutic decision-making and clinical trial enrollment. We implemented prospective next-generation sequencing (NGS) the clinic to determine whether such analyses provide predictive and/or prognostic information for HCC patients treated with contemporary systemic therapies. Experimental Design: Matched tumor/normal DNA from (N = 127) were analyzed...
Purpose A long natural history and a predominant osseous pattern of metastatic spread are impediments to the adoption precision medicine in patients with prostate cancer. To establish feasibility clinical genomic profiling this disease, we performed targeted deep sequencing tumor normal DNA from locoregional, noncastrate, castration-resistant Patients Methods consented analysis their germline DNA. hybridization capture-based assay was used identify single-nucleotide variations, small...
Hippo signaling has been recognized as a key tumor suppressor pathway. Here, we perform comprehensive molecular characterization of 19 core genes in 9,125 samples across 33 cancer types using multidimensional "omic" data from The Cancer Genome Atlas. We identify somatic drivers among and the related microRNA (miRNA) regulators, functional genomic approaches, experimentally characterize YAP TAZ mutation effects miR-590 miR-200a regulation for TAZ. pathway activity is best characterized by...
We characterized the epigenetic landscape of genes encoding long noncoding RNAs (lncRNAs) across 6,475 tumors and 455 cancer cell lines. In stark contrast to CpG island hypermethylation phenotype in cancer, we observed a recurrent hypomethylation 1,006 lncRNA including EPIC1 (epigenetically-induced lncRNA1). Overexpression is associated with poor prognosis luminal B breast patients enhances tumor growth vitro vivo. Mechanistically, promotes cell-cycle progression by interacting MYC through...
Hotspot mutations in splicing factor genes have been recently reported at high frequency hematological malignancies, suggesting the importance of RNA cancer. We analyzed whole-exome sequencing data across 33 tumor types The Cancer Genome Atlas (TCGA), and we identified 119 with significant non-silent mutation patterns, including over-representation, recurrent loss function (tumor suppressor-like), or hotspot profile (oncogene-like). Furthermore, analysis revealed altered events associated...
We studied 137 primary testicular germ cell tumors (TGCTs) using high-dimensional assays of genomic, epigenomic, transcriptomic, and proteomic features. These exhibited high aneuploidy a paucity somatic mutations. Somatic mutation only three genes achieved significance—KIT, KRAS, NRAS—exclusively in samples with seminoma components. Integrated analyses identified distinct molecular patterns that characterized the major recognized histologic subtypes TGCT: seminoma, embryonal carcinoma, yolk...
Highlights•MYC paralogs are significantly amplified (28% of all samples)•MYC antagonists mutated (MGA, 4% samples) or deleted (MNT, 10% alterations mutually exclusive with PIK3CA, PTEN, APC, BRAF alterations•Expression analysis reveals pan-cancer and tumor-specific MYC-associated pathwaysSummaryAlthough the MYC oncogene has been implicated in cancer, a systematic assessment MYC, related transcription factors, co-regulatory proteins, forming proximal network (PMN), across human cancers is...