Nicola D. Roberts
A5013477931- Cancer Genomics and Diagnostics
- Genetic factors in colorectal cancer
- Genomics and Chromatin Dynamics
- Genomic variations and chromosomal abnormalities
- Chromosomal and Genetic Variations
- Genomics and Phylogenetic Studies
- Evolution and Genetic Dynamics
- Bioinformatics and Genomic Networks
- Epigenetics and DNA Methylation
- RNA modifications and cancer
- DNA Repair Mechanisms
- Chronic Lymphocytic Leukemia Research
- Cancer-related molecular mechanisms research
- Genetic Associations and Epidemiology
- Cancer-related gene regulation
- Chronic Myeloid Leukemia Treatments
- Genomics and Rare Diseases
- Nutrition, Genetics, and Disease
- Lung Cancer Treatments and Mutations
- Mitochondrial Function and Pathology
- RNA Research and Splicing
- Plant Disease Resistance and Genetics
- Telomeres, Telomerase, and Senescence
- Genetics, Bioinformatics, and Biomedical Research
- Cancer, Hypoxia, and Metabolism
Wellcome Sanger Institute
2016-2023
University of Cambridge
2014-2023
Mayo Clinic in Arizona
2020
Addenbrooke's Hospital
2015
Centre for Cancer Biology
2013-2014
South Australia Pathology
2013-2014
The University of Adelaide
2013
University of Bradford
1980
Recent studies have provided a detailed census of genes that are mutated in acute myeloid leukemia (AML). Our next challenge is to understand how this genetic diversity defines the pathophysiology AML and informs clinical practice.
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...
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...
The discovery of drivers cancer has traditionally focused on protein-coding genes
Abstract About half of all cancers have somatic integrations retrotransposons. Here, to characterize their role in oncogenesis, we analyzed the patterns and mechanisms retrotransposition 2,954 cancer genomes from 38 histological subtypes within framework Pan-Cancer Analysis Whole Genomes (PCAWG) project. We identified 19,166 somatically acquired events, which affected 35% samples spanned a range event types. Long interspersed nuclear element (LINE-1; L1 hereafter) insertions emerged as first...
Abstract Ionizing radiation is a potent carcinogen, inducing cancer through DNA damage. The signatures of mutations arising in human tissues following vivo exposure to ionizing have not been documented. Here, we searched for 12 radiation-associated second malignancies different tumour types. Two somatic mutation characterize irrespective type. Compared with 319 radiation-naive tumours, tumours carry median extra 201 deletions genome-wide, sized 1–100 base pairs often microhomology at the...
Chromatin is folded into successive layers to organize linear DNA. Genes within the same topologically associating domains (TADs) demonstrate similar expression and histone-modification profiles, boundaries separating different have important roles in reinforcing stability of these features. Indeed, domain disruptions human cancers can lead misregulation gene expression. However, frequency remains unclear. Here, as part Pan-Cancer Analysis Whole Genomes (PCAWG) Consortium International...
Looping together genes in cancer A subset of human cancers are characterized by aberrant fusion two specific genes. In some cases, the activity resultant protein drives tumor growth. Most appear to arise from simple reciprocal chromosomal translocations. Anderson et al. found that characteristic gene a bone and soft tissue called Ewing sarcoma is produced far more complicated mechanism (see Perspective Imielinski Ladanyi). nearly half tumors examined, was created formation dramatic genomic...
Abstract The major genetic determinants of cutaneous melanoma risk in the general population are disruptive variants ( R alleles) melanocortin 1 receptor MC1R ) gene. These alleles also linked to red hair, freckling, and sun sensitivity, all which known phenotypic factors. Here we report that melanomas for somatic C>T mutations, a signature exposure, expected single-nucleotide variant count associated with presence an allele is estimated be 42% (95% CI, 15–76%) higher than among persons...
Abstract Cancers require telomere maintenance mechanisms for unlimited replicative potential. They achieve this through TERT activation or alternative lengthening associated with ATRX DAXX loss. Here, as part of the ICGC/TCGA Pan-Cancer Analysis Whole Genomes (PCAWG) Consortium , we dissect whole-genome sequencing data over 2500 matched tumor-control samples from 36 different tumor types aggregated within to characterize genomic footprints these mechanisms. While content tumors mutations...
With the advent of relatively affordable high-throughput technologies, DNA sequencing cancers is now common practice in cancer research projects and will be increasingly used clinical to inform diagnosis treatment. Somatic (cancer-only) single nucleotide variants (SNVs) are simplest class mutation, yet their identification data confounded by germline polymorphisms, tumour heterogeneity analysis errors. Four recently published algorithms for detection somatic SNV sites matched cancer-normal...
ABSTRACT A key mutational process in cancer is structural variation, which rearrangements delete, amplify or reorder genomic segments ranging size from kilobases to whole chromosomes. We developed methods group, classify and describe variants, applied >2,500 genomes. Nine signatures of variation emerged. Deletions have trimodal distribution; assort unevenly across tumour types patients; enrich late-replicating regions; correlate with inversions. Tandem duplications also distribution, but...
Whether cell types exposed to a high level of environmental insults possess type-specific prosurvival mechanisms or enhanced DNA damage repair capacity is not well understood. BRN2 tissue-restricted POU domain transcription factor implicated in neural development and several cancers. In melanoma, plays key role promoting invasion regulating proliferation. Here we found, surprisingly, that rather than interacting with cofactors, instead associated response proteins directly binds PARP1...
Abstract Cancer cells can acquire profound alterations to the structure of their genomes, including rearrangements that fuse distant DNA breakpoints. We analyze distribution somatic across cancer genome, using whole-genome sequencing data from 2,693 tumor-normal pairs. observe substantial variation in density rearrangement breakpoints, with enrichment open chromatin and sites high densities repetitive elements. After accounting for these patterns, we identify significantly recurrent...
Abstract About half of all cancers have somatic integrations retrotransposons. To characterize their role in oncogenesis, we analyzed the patterns and mechanisms retrotransposition 2,954 cancer genomes from 37 histological subtypes. We identified 19,166 somatically acquired events, affecting 35% samples, spanning a range event types. L1 insertions emerged as first most frequent type structural variation esophageal adenocarcinoma, second head-and-neck colorectal cancers. Aberrant can delete...