Azhar Khandekar
A5065342854- Cancer Genomics and Diagnostics
- Epigenetics and DNA Methylation
- Genetic factors in colorectal cancer
- RNA modifications and cancer
- Lung Cancer Treatments and Mutations
- DNA Repair Mechanisms
- Genomics and Rare Diseases
- Genomics and Phylogenetic Studies
- Genomic variations and chromosomal abnormalities
- Occupational and environmental lung diseases
- Medical Imaging and Pathology Studies
- Conflict Management and Negotiation
- Evolution and Genetic Dynamics
- Glycosylation and Glycoproteins Research
- Cancer-related molecular mechanisms research
- Pancreatic and Hepatic Oncology Research
- Cell Image Analysis Techniques
- Renal cell carcinoma treatment
- Esophageal Cancer Research and Treatment
- Counseling Practices and Supervision
- Genomics and Chromatin Dynamics
- Medical Malpractice and Liability Issues
- CRISPR and Genetic Engineering
- Single-cell and spatial transcriptomics
- PARP inhibition in cancer therapy
University of California, San Diego
2020-2025
La Jolla Bioengineering Institute
2020-2024
National Cancer Institute
2024
National Institutes of Health
2024
UC San Diego Health System
2021
University of Washington
2017
Abstract Gains and losses of DNA are prevalent in cancer emerge as a consequence inter-related processes replication stress, mitotic errors, spindle multipolarity breakage–fusion–bridge cycles, among others, which may lead to chromosomal instability aneuploidy 1,2 . These copy number alterations contribute initiation, progression therapeutic resistance 3–5 Here we present conceptual framework examine the patterns human that is widely applicable diverse data types, including whole-genome...
Mutational signature analysis is commonly performed in cancer genomic studies. Here, we present SigProfilerExtractor, an automated tool for
Clustered somatic mutations are common in cancer genomes and previous analyses reveal several types of clustered single-base substitutions, which include doublet- multi-base substitutions
Abstract Malignant pleural mesothelioma (MPM) is an aggressive cancer with rising incidence and challenging clinical management. Through a large series of whole-genome sequencing data, integrated transcriptomic epigenomic data using multiomics factor analysis, we demonstrate that the current World Health Organization classification only accounts for up to 10% interpatient molecular differences. Instead, MESOMICS project paves way morphomolecular MPM based on four dimensions: ploidy, tumor...
Abstract International differences in the incidence of many cancer types indicate existence carcinogen exposures that have not yet been identified by conventional epidemiology make a substantial contribution to burden 1 . In clear cell renal carcinoma, obesity, hypertension and tobacco smoking are risk factors, but they do explain geographical variation its 2 Underlying causes can be inferred sequencing genomes cancers from populations with different rates detecting patterns somatic...
SUMMARY Mutational signature analysis is commonly performed in genomic studies surveying cancer and normal somatic tissues. Here we present SigProfilerExtractor, an automated tool for accurate de novo extraction of mutational signatures all types mutations. Benchmarking with a total 34 distinct scenarios encompassing 2,500 simulated operative more than 60,000 unique synthetic genomes 20,000 exomes demonstrates that SigProfilerExtractor outperforms thirteen other tools across datasets without...
ABSTRACT Colorectal cancer incidence rates vary geographically and have changed over time. Notably, in the past two decades, of early-onset colorectal cancer, affecting individuals under age 50 years, has doubled many countries. The reasons for this increase are unknown. Here, we investigate whether mutational processes contribute to geographic age-related differences by examining 981 genomes from 11 No major were found microsatellite unstable cancers, but variations mutation burden...
Understanding lung cancer evolution can identify tools for intercepting its growth. In a landscape analysis of 1024 adenocarcinomas (LUAD) with deep whole-genome sequencing integrated multi-omic data, we identified 542 LUAD that displayed diverse clonal architecture. this group, observed an interplay between mobile elements, endogenous and exogenous mutational processes, distinct driver genes, epidemiological features. Our results revealed divergent evolutionary trajectories based on tobacco...
All cancers harbor somatic mutations in their genomes. In principle, affecting between one and fifty base pairs are generally classified as small mutational events. Conversely, large events affect more than pairs, and, most cases, they encompass copy-number structural variants many thousands of pairs. Prior studies have demonstrated that examining patterns can be leveraged to provide both biological clinical insights, thus, resulting an extensive repertoire tools for evaluating Recently,...
ABSTRACT Lung cancer in never smokers (LCINS) accounts for up to 25% of all lung cancers and has been associated with exposure secondhand tobacco smoke air pollution observational studies. Here, we evaluate the mutagenic exposures LCINS by examining deep whole-genome sequencing data from a large international cohort 871 treatment-naïve recruited 28 geographical locations within Sherlock- study. KRAS mutations were 3.8-fold more common adenocarcinomas North America Europe, while 1.6-fold...
Breast and ovarian cancers harboring homologous recombination deficiency (HRD) are sensitive to PARP inhibitors platinum chemotherapy. Conventionally, detecting HRD involves screening for defects in BRCA1, BRCA2, other relevant genes. Recent analyses have shown that exhibit characteristic mutational patterns due the activities of HRD-associated signatures. At least three machine learning tools exist based on patterns. Here, using sequencing data from 1,043 breast 182 cancers, we trained...
All cancers harbor somatic mutations in their genomes. In principle, affecting between one and fifty base pairs are generally classified as small mutational events. Conversely, large events affect more than pairs, and, most cases, they encompass copy-number structural variants many thousands of pairs. Prior studies have demonstrated that examining patterns can be leveraged to provide both biological clinical insights, thus, resulting an extensive repertoire tools for evaluating Recently,...
ABSTRACT The gains and losses of DNA that emerge as a consequence mitotic errors chromosomal instability are prevalent in cancer. These copy number alterations contribute to cancer initiaition, progression therapeutic resistance. Here, we present conceptual framework for examining the patterns human using whole-genome sequencing, whole-exome SNP6 microarray data making it widely applicable diverse datasets. Deploying this 9,873 cancers representing 33 types from TCGA project revealed set 19...
Abstract Esophageal squamous cell carcinoma (ESCC) shows a remarkable variation in incidence which is not fully explained by known lifestyle and environmental risk factors. It has been speculated that an unknown exogenous exposure(s) could be responsible. Here we combine the fields of mutational signature analysis with cancer epidemiology to study 552 ESCC genomes from eight countries varying rates. The profiles were similar across all studied. Associations between specific signatures...
Abstract The development of mutational signatures defined individually in the contexts single/double base substitutions, insertions and deletions, structural variants copy number variation have led to improved understanding cancer mutagenesis potential for patient stratification. We hypothesized that combining these into a multi-modal signature framework may improve accuracy assigning processes samples, provide holistic view full repertoire mutations conferred from such processes. In order...
Abstract Lung cancer is the leading cause of cancer-related mortality worldwide. Understanding lung evolutionary dynamics can help identify tools to intercept its growth and suggest strategies for treatment. Multiple factors impact tumors’ natural history distinctly affect rate. However, research on trajectories across demographic or exposure scenarios remains inadequate. Additionally, roles mutational processes complex genomic alterations evolution are still largely unexplored. In largest...
Abstract While most lung cancers are associated with tobacco smoking, prior studies have indicated that 15-20% of cases found in never smokers. Lung cancer smokers (LCINS) shows demographic variations, being more common females and Asian populations. Epidemiological also identified environmental risk factors for LCINS, including exposure to secondhand smoke air pollution. As part the Sherlock-Lung project (current data freeze 1217 samples), we generated deep WGS from a large international...
Abstract Extrachromosomal DNA (ecDNA), circular that resides outside of the linear chromosome, is a potent form oncogene amplification in cancer. The structure and properties ecDNA are markedly different from those DNA, characterized by features like non-Mendelian inheritance an altered epigenetic landscape. A prior pan-cancer analysis indicated patients with cancers harboring have statistically worse overall survival when compared to cancer other types focal amplification. Moreover, its...
Summary Malignant Pleural Mesothelioma (MPM) is an aggressive cancer with rising incidence and challenging clinical management. Using the largest series of whole-genome sequencing data integrated transcriptomic epigenomic using multi-omic factor analysis, we demonstrate that MPM heterogeneity arises from four sources variation: tumor cell morphology, ploidy, adaptive immune response, CpG island methylator phenotype. Previous genomic studies focused on describing only morphology factor,...
ABSTRACT International differences in the incidence of many cancer types indicate existence carcinogen exposures that have not been identified by conventional epidemiology yet potentially make a substantial contribution to burden 1 . This pertains clear cell renal carcinoma (ccRCC), for which obesity, hypertension, and tobacco smoking are risk factors but do explain its geographical variation 2 Some carcinogens generate somatic mutations complementary strategy detecting past is sequence...