Nicolai J. Birkbak
A5080932242- Cancer Genomics and Diagnostics
- DNA Repair Mechanisms
- RNA modifications and cancer
- Gene expression and cancer classification
- Lung Cancer Treatments and Mutations
- Cancer Immunotherapy and Biomarkers
- PARP inhibition in cancer therapy
- Bioinformatics and Genomic Networks
- Genetic factors in colorectal cancer
- Epigenetics and DNA Methylation
- BRCA gene mutations in cancer
- Genomic variations and chromosomal abnormalities
- Bladder and Urothelial Cancer Treatments
- Genetics and Neurodevelopmental Disorders
- Immunotherapy and Immune Responses
- Ferroptosis and cancer prognosis
- Microtubule and mitosis dynamics
- Genetics, Bioinformatics, and Biomedical Research
- Molecular Biology Techniques and Applications
- RNA Interference and Gene Delivery
- Genomics and Phylogenetic Studies
- CRISPR and Genetic Engineering
- Evolution and Genetic Dynamics
- Computational Drug Discovery Methods
- Genomics and Chromatin Dynamics
Cancer Research UK
2011-2025
Aarhus University
2019-2025
London Cancer
2015-2025
CRUK Lung Cancer Centre of Excellence
2015-2025
University College London
2015-2025
Aarhus University Hospital
2019-2025
The Francis Crick Institute
2015-2025
Technical University of Denmark
2011-2023
Dana-Farber Cancer Institute
2011-2023
Cancer Institute (WIA)
2017-2023
The cellular ancestry of tumor antigens One contributing factor in antitumor immunity is the repertoire neoantigens created by genetic mutations within cells. Like corresponding mutations, these show intratumoral heterogeneity. Some are present all cells (clonal), and others only a fraction (subclonal). In study lung cancer melanoma, McGranahan et al. found that high burden clonal correlated with improved patient survival, an increased presence tumor-infiltrating lymphocytes, durable...
Among patients with non-small-cell lung cancer (NSCLC), data on intratumor heterogeneity and genome evolution have been limited to small retrospective cohorts. We wanted prospectively investigate in relation clinical outcome determine the clonal nature of driver events evolutionary processes early-stage NSCLC.
Immune evasion is a hallmark of cancer. Losing the ability to present neoantigens through human leukocyte antigen (HLA) loss may facilitate immune evasion. However, polymorphic nature locus has precluded accurate HLA copy-number analysis. Here, we heterozygosity in (LOHHLA), computational tool determine allele-specific copy number from sequencing data. Using LOHHLA, find that LOH occurs 40% non-small-cell lung cancers (NSCLCs) and associated with high subclonal neoantigen burden,...
The focus of tumour-specific antigen analyses has been on single nucleotide variants (SNVs), with the contribution small insertions and deletions (indels) less well characterised. We investigated whether frameshift nature indel mutations, which create novel open reading frames a large quantity mutagenic peptides highly distinct from self, might contribute to immunogenic phenotype.
Exome or whole-genome deep sequencing of tumor DNA along with paired normal can potentially provide a detailed picture the somatic mutations that characterize tumor. However, analysis such sequence data be complicated by presence cells in specimen, intratumor heterogeneity, and sheer size raw data. In particular, determination copy number variations from exome alone has proven difficult; thus, single nucleotide polymorphism (SNP) arrays have often been used for this task. Recently,...
Deciphering whether actionable driver mutations are found in all or a subset of tumor cells will likely be required to improve drug development and precision medicine strategies. We analyzed nine cancer types determine the subclonal frequencies events, time mutational processes during evolution, identify drivers expansions. Although known genes typically occurred early we also identified later "actionable" mutations, including BRAF (V600E), IDH1 (R132H), PIK3CA (E545K), EGFR (L858R), KRAS...
DNA repair competency is one determinant of sensitivity to certain chemotherapy drugs, such as cisplatin. Cancer cells with intact can avoid the accumulation genome damage during growth and also platinum-induced damage. We sought genomic signatures indicative defective in cell lines tumors correlated these platinum sensitivity. The number subchromosomal regions allelic imbalance extending telomere (N(tAI)) predicted cisplatin vitro pathologic response preoperative treatment patients...
The evolutionary features of clear-cell renal cell carcinoma (ccRCC) have not been systematically studied to date. We analyzed 1,206 primary tumor regions from 101 patients recruited into the multi-center prospective study, TRACERx Renal. observe up 30 driver events per and show that subclonal diversification is associated with known prognostic parameters. By resolving patterns event ordering, co-occurrence, mutual exclusivity at clone level, we deterministic nature clonal evolution. ccRCC...
Aneuploidy is associated with poor prognosis in solid tumors. Spontaneous chromosome missegregation events aneuploid cells promote chromosomal instability (CIN) that may contribute to the acquisition of multidrug resistance vitro and heighten risk for tumor relapse animal models. Identification distinct therapeutic agents target karyotypic complexity has important clinical implications. To identify approaches specifically limit growth CIN tumors, we focused on a panel colorectal cancer (CRC)...
IntroductionImmunotherapy is regarded as one of the major breakthroughs in cancer treatment. Despite its success, only a subset patients responds—urging quest for predictive biomarkers. We hypothesize that artificial intelligence (AI) algorithms can automatically quantify radiographic characteristics are related to and may therefore act noninvasive radiomic biomarkers immunotherapy response.Patients methodsIn this study, we analyzed 1055 primary metastatic lesions from 203 with advanced...
CD25 is expressed at high levels on regulatory T (Treg) cells and was initially proposed as a target for cancer immunotherapy. However, anti-CD25 antibodies have displayed limited activity against established tumors. We demonstrated that expression largely restricted to tumor-infiltrating Treg in mice humans. While existing were observed deplete the periphery, upregulation of inhibitory Fc gamma receptor (FcγR) IIb tumor site prevented intra-tumoral cell depletion, which may underlie lack...
Chromosomal instability (CIN) is associated with poor prognosis in human cancer. However, certain animal tumor models elevated CIN negatively impacts upon organism fitness, and poorly tolerated by cancer cells. To better understand this seemingly contradictory relationship between cell biological fitness its clinical outcome, we applied the CIN70 expression signature, which correlates DNA-based measures of structural chromosomal complexity numerical vivo, to gene profiles 2,125 breast tumors...
Abstract Background Interpretation of gene expression microarrays requires a mapping from probe set to gene. On many Affymetrix microarrays, given may be detected by multiple sets, which deliver inconsistent or even contradictory measurements. Therefore, obtaining an unambiguous estimate pre-specified can nontrivial but essential task. Results We developed scoring methods assess each for specificity, splice isoform coverage, and robustness against transcript degradation. used these scores...
Abstract The molecular landscape in non-muscle-invasive bladder cancer (NMIBC) is characterized by large biological heterogeneity with variable clinical outcomes. Here, we perform an integrative multi-omics analysis of patients diagnosed NMIBC ( n = 834). Transcriptomic identifies four classes (1, 2a, 2b and 3) reflecting tumor biology disease aggressiveness. Both transcriptome-based subtyping the level chromosomal instability provide independent prognostic value beyond established...
Ovarian and triple-negative breast cancers with BRCA1 or BRCA2 loss are highly sensitive to treatment PARP inhibitors platinum-based cytotoxic agents show an accumulation of genomic scars in the form gross DNA copy number aberrations. Cancers without but similar also increased sensitivity chemotherapy. Therefore, reliable biomarkers identify repair-deficient prior may be useful for directing patients platinum chemotherapy possibly inhibitors. Recently, three SNP array-based signatures...
Esophageal adenocarcinomas are associated with a dismal prognosis. Deciphering the evolutionary history of this disease may shed light on therapeutically tractable targets and reveal dynamic mutational processes during course following neoadjuvant chemotherapy (NAC). We exome sequenced 40 tumor regions from 8 patients operable esophageal adenocarcinomas, before after platinum-containing NAC. This revealed genomic landscape presence heterogeneous driver mutations, parallel evolution, early...
The first genomic scar-based homologous recombination deficiency (HRD) measures were produced using SNP arrays. As array-based technology has been largely replaced by next generation sequencing approaches, it become important to develop algorithms that derive the same type of scar scores from (whole exome "WXS", whole genome "WGS") data. In order perform this analysis, we introduce here scarHRD R package and show method sequencing-based derivation HRD good correlation (Pearson between 0.73...