Hikmat Al‐Ahmadie
A5022477189- Bladder and Urothelial Cancer Treatments
- Urinary and Genital Oncology Studies
- Cancer Genomics and Diagnostics
- Epigenetics and DNA Methylation
- Cancer Immunotherapy and Biomarkers
- Renal cell carcinoma treatment
- Genetic factors in colorectal cancer
- Ferroptosis and cancer prognosis
- Prostate Cancer Treatment and Research
- Urological Disorders and Treatments
- Renal and related cancers
- Peptidase Inhibition and Analysis
- Prostate Cancer Diagnosis and Treatment
- Immune cells in cancer
- Multiple and Secondary Primary Cancers
- Fibroblast Growth Factor Research
- Testicular diseases and treatments
- Neuroendocrine Tumor Research Advances
- Lung Cancer Research Studies
- Lung Cancer Treatments and Mutations
- Esophageal Cancer Research and Treatment
- Urologic and reproductive health conditions
- Cancer, Hypoxia, and Metabolism
- Cancer, Lipids, and Metabolism
- Immune responses and vaccinations
Memorial Sloan Kettering Cancer Center
2016-2025
Kettering University
2011-2025
Queen Mary University of London
2024
University of Sheffield
2024
Barts Health NHS Trust
2024
Sheffield Teaching Hospitals NHS Foundation Trust
2024
Weatherford College
2023
Cleveland Clinic
2013-2022
NorthShore University HealthSystem
2022
Michigan Medicine
2014-2022
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...
Urothelial carcinoma of the bladder is a common malignancy that causes approximately 150,000 deaths per year worldwide. So far, no molecularly targeted agents have been approved for treatment disease. As part The Cancer Genome Atlas project, we report here an integrated analysis 131 urothelial carcinomas to provide comprehensive landscape molecular alterations. There were statistically significant recurrent mutations in 32 genes, including multiple genes involved cell-cycle regulation,...
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...
Abstract A key mutational process in cancer is structural variation, which rearrangements delete, amplify or reorder genomic segments that range size from kilobases to whole chromosomes 1–7 . Here we develop methods group, classify and describe somatic variants, using data the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium International Cancer Genome (ICGC) The Atlas (TCGA), aggregated whole-genome sequencing 2,658 cancers across 38 tumour types 8 Sixteen signatures variation...
Cancer drugs often induce dramatic responses in a small minority of patients. We used whole-genome sequencing to investigate the genetic basis durable remission metastatic bladder cancer patient treated with everolimus, drug that inhibits mTOR (mammalian target rapamycin) signaling pathway. Among somatic mutations was loss-of-function mutation TSC1 (tuberous sclerosis complex 1), regulator pathway activation. Targeted revealed about 8% 109 additional cancers examined, and correlated...
Chromothripsis is a mutational phenomenon characterized by massive, clustered genomic rearrangements that occurs in cancer and other diseases. Recent studies selected types have suggested chromothripsis may be more common than initially inferred from low-resolution copy-number data. Here, as part of the Pan-Cancer Analysis Whole Genomes (PCAWG) Consortium International Cancer Genome (ICGC) The Atlas (TCGA), we analyze patterns across 2,658 tumors 38 using whole-genome sequencing We find...
Cisplatin-based chemotherapy is the standard of care for patients with muscle-invasive urothelial carcinoma. Pathologic downstaging to pT0/pTis after neoadjuvant cisplatin-based associated improved survival, although molecular determinants cisplatin response are incompletely understood. We performed whole-exome sequencing on pretreatment tumor and germline DNA from 50 carcinoma who received followed by cystectomy (25 "responders," 25 pT2+ "nonresponders") identify somatic mutations that...
Purpose Alterations in DNA damage response and repair (DDR) genes are associated with increased mutation load improved clinical outcomes platinum-treated metastatic urothelial carcinoma. We examined the relationship between DDR alterations to PD-1/PD-L1 blockade. Methods Detailed demographic, treatment response, long-term outcome data were collected on patients carcinoma treated atezolizumab or nivolumab who had targeted exon sequencing performed pre-immunotherapy tumor specimens. Presence...
Mutations, deletions, and changes in copy number of mitochondrial DNA (mtDNA), are observed throughout cancers. Here, we survey mtDNA variation across 22 tumor types profiled by The Cancer Genome Atlas project. We observe a tendency for some cancers, especially the bladder, breast, kidney, to be depleted mtDNA, relative matched normal tissue. Analysis genetic context reveals an association between incidence several somatic alterations, including IDH1 mutations gliomas, content. In but not...
B7-H3 and B7x are recently discovered members of the B7-CD28 family thought to dampen peripheral immune responses via negative costimulation. We evaluated their potential expression in human prostate cancer using a large cohort patients with 7 years follow-up. identified 823 tissue available treated radical prostatectomy between 1985 2003. Immunohistochemistry was performed on microarray sections anti-B7-H3 -B7x. The percentage intensity immunoreactivity by tumor cells were blindly two...
Abstract Here, as part of the Pan-Cancer Analysis Whole Genomes (PCAWG) Consortium, for which whole-genome and—for a subset—whole-transcriptome sequencing data from 2,658 cancers across 38 tumor types was aggregated, we systematically investigated potential viral pathogens using consensus approach that integrated three independent pipelines. Viruses were detected in 382 genome and 68 transcriptome datasets. We found high prevalence known tumor-associated viruses such Epstein–Barr virus...
Mitochondria are essential cellular organelles that play critical roles in cancer. Here, as part of the International Cancer Genome Consortium/The Atlas Pan-Cancer Analysis Whole Genomes Consortium, which aggregated whole-genome sequencing data from 2,658 cancers across 38 tumor types, we performed a multidimensional, integrated characterization mitochondrial genomes and related RNA data. Our analysis presents most definitive mutational landscape identifies several hypermutated cases....
Approximately 50% of conventional inflammatory myofibroblastic tumors (IMTs) harbor ALK gene rearrangement and overexpress ALK. Recently, fusions involving other kinases have been implicated in the pathogenesis IMT, including ROS1 1 patient PDGFRB. However, it remains uncertain whether emerging genotypes correlate with clinicopathologic characteristics IMT. In this study, we expand molecular investigation IMT a large cohort different clinical presentations analyze for potential...
Background Inhibition of programmed death-ligand 1 (PD-L1) with atezolizumab can induce durable clinical benefit (DCB) in patients metastatic urothelial cancers, including complete remissions chemotherapy refractory disease. Although mutation load and PD-L1 immune cell (IC) staining have been associated response, they lack sufficient sensitivity specificity for use. Thus, there is a need to evaluate the peripheral blood environment conduct detailed analyses load, predicted neoantigens,...
Highlights•SCCs show chromosome or methylation alterations affecting multiple related genes•These regulate squamous stemness, differentiation, growth, survival, and inflammation•Copy-quiet SCCs have hypermethylated (FANCF, TET1) mutated (CASP8, MAPK-RAS) genes•Potential targets include ΔNp63, WEE1, IAPs, PI3K-mTOR/MAPK, immune responsesSummaryThis integrated, multiplatform PanCancer Atlas study co-mapped identified distinguishing molecular features of cell carcinomas (SCCs) from five sites...
Purpose We sought to define the prevalence and co-occurrence of actionable genomic alterations in patients with high-grade bladder cancer serve as a platform for therapeutic drug discovery. Patients Methods An integrative analysis 97 tumors was conducted identify targets, which are defined that have been clinically validated another type (eg, BRAF mutation) or selective inhibitor target pathway is under clinical investigation. DNA copy number (CNAs) were by using array comparative...
Purpose: Platinum-based chemotherapy remains the standard treatment for advanced urothelial carcinoma by inducing DNA damage. We hypothesize that somatic alterations in damage response and repair (DDR) genes are associated with improved sensitivity to platinum-based chemotherapy.Experimental Design: Patients diagnosis of locally metastatic treated who had exon sequencing Memorial Sloan Kettering-Integrated Mutation Profiling Actionable Cancer Targets (MSK-IMPACT) assay were identified....
Hereditary leiomyomatosis and renal cell carcinoma (HLRCC) syndrome is an autosomal dominant disorder in which germline mutations of fumarate hydratase (FH) gene confer increased risk cutaneous uterine leiomyomas cancer. HLRCC-associated cancer highly aggressive frequently presents as a solitary mass. We reviewed the clinicopathologic features 9 patients with tumors presenting sporadic cases but who were later proven to have FH mutations. Histologically, all showed mixed architectural...