A5076004822- Cancer Genomics and Diagnostics
- Genetic factors in colorectal cancer
- RNA modifications and cancer
- Cancer-related molecular mechanisms research
- RNA Research and Splicing
- Prostate Cancer Treatment and Research
- Colorectal Cancer Treatments and Studies
- Prostate Cancer Diagnosis and Treatment
- Cancer, Lipids, and Metabolism
- Molecular Biology Techniques and Applications
- Ovarian cancer diagnosis and treatment
- Genomics and Phylogenetic Studies
- Genetic and Clinical Aspects of Sex Determination and Chromosomal Abnormalities
- Lymphoma Diagnosis and Treatment
- Testicular diseases and treatments
- RNA and protein synthesis mechanisms
- Magnesium in Health and Disease
- Lung Cancer Treatments and Mutations
- Cancer Cells and Metastasis
- Genomic variations and chromosomal abnormalities
- Cancer-related Molecular Pathways
- Gene expression and cancer classification
- Mycobacterium research and diagnosis
- Parathyroid Disorders and Treatments
- Congenital heart defects research
Oslo University Hospital
2015-2024
Norwegian Cancer Society
2023
Oslo Cancer Cluster
2018-2022
University of Oslo
1969-2020
Institute of Clinical Research
2020
Colorectal cancer (CRC) cell lines are widely used pre-clinical model systems. Comprehensive insights into their molecular characteristics may improve selection for biomedical studies. We have performed DNA, RNA and protein profiling of 34 lines, including (i) targeted deep sequencing (n = 612 genes) to detect single nucleotide variants insertions/deletions; (ii) high resolution DNA copy number profiling; (iii) gene expression at exon resolution; (iv) small by sequencing; (v) analysis 297...
Approximately 15% of primary colorectal cancers have DNA mismatch repair deficiency, causing a complex genome with thousands small mutations-the microsatellite instability (MSI) phenotype. We investigated molecular heterogeneity and tumor immunogenicity in relation to clinical endpoints within this distinct subtype cancers.
// Jennifer Munkley 1 , Sebastian Oltean 2 Daniel Vodák 3 Brian T. Wilson Karen E. Livermore Yan Zhou 5 ,Eleanor Star Vasileios I. Floros Bjarne Johannessen 6 Bridget Knight 7 Paul McCullagh 8 John McGrath 9 Malcolm Crundwell 10 Rolf Skotheim Craig N. Robson 11 Hing Y. Leung 5,12 Lorna W. Harries 13 Prabhakar Rajan Ian G. Mills 14,15,16 and David J. Elliott Institute of Genetic Medicine, Newcastle University, Newcastle-upon-Tyne, UK Microvascular Research Laboratories, School Physiology...
Summary Two brothers are reported, who at the ages of two and three weeks respectively, demonstrated generalized tetanic convulsions. In both cases, hypocalcemia hypophosphatemia were found. The serum magnesium elder brother was not determined, whereas younger found to have severe hypomag‐nesemia. Calcium administration had no effect on condition one, died age 50 days. younger, alone led a normalization clinical as well biochemical picture. On daily oral supplementation, child is healthy...
In breast cancer, activation of bone morphogenetic protein (BMP) signaling and elevated levels BMP-antagonists have been linked to tumor progression metastasis. However, the simultaneous upregulation BMPs their antagonist, fact that both promote aggressiveness seems contradictory is not fully understood.We analyzed transcriptomes metastatic 66cl4 non-metastatic 67NR cell lines 4T1 mouse mammary model search for factors CRISPR/Cas9 gene editing was used mechanistic studies in same lines....
BackgroundPARP inhibitors are active in various tumour types beyond BRCA-mutant cancers, but their activity and molecular correlates colorectal cancer (CRC) not well studied.MethodsMutations genome-wide mutational patterns associated with homologous recombination deficiency (HRD) were investigated 255 primary CRCs whole-exome sequencing and/or DNA copy number data. Efficacy of five PARP evaluated 93 CRC cell lines partly annotated mutational-, number-, gene expression profiles....
Abstract TP53 mutations are common in colorectal cancer (CRC). Most sequencing studies have been restricted to coding regions, but recent revealed that splice can generate transcript variants with distinct tumorigenic and prognostic properties. Here, we performed unrestricted of all sequences regions a single-hospital series 401 primary CRCs. were detected 4% the cases ( N = 16), considerably more frequent than reported major databases, they mutually exclusive exon mutations. RNA high-level...
Abstract Summary Advances in high-throughput RNA sequencing have enabled more efficient detection of fusion transcripts, but the technology and associated software used for from data often yield a high false discovery rate. Good prioritization results is important, this can be helped by visualization framework that automatically integrates with known genomic features. Here we present chimeraviz, Bioconductor package automates creation chimeric visualizations. The supports input nine...
A fusion gene is a hybrid consisting of parts from two previously independent genes. Chromosomal rearrangements leading to breakage are frequent in high-grade serous ovarian carcinomas and have been reported as common mechanism for inactivating tumor suppressor However, no genes repeatedly be recurrent driver events carcinogenesis. We combined genomic transcriptomic information identify novel candidates aberrantly expressed carcinomas.Examined were 19 karyotyped (18 the histotype one...
BackgroundThe prevalence and clinical implications of genetic heterogeneity in patients with multiple colorectal liver metastases remain largely unknown. In a prospective series undergoing resection metastases, the aim was to investigate inter-metastatic primary-to-metastatic mutations KRAS, NRAS, BRAF, PIK3CA their prognostic impact.Patients MethodsWe analyzed mutation status among 372 78 primary tumors from 106 by methods used routine testing, Sanger sequencing, next-generation sequencing...
Many breast cancer patients are diagnosed with small, well-differentiated, hormone receptor-positive tumors. Risk of relapse is not easily identified in these patients, resulting overtreatment. To identify metastasis-related gene expression patterns, we compared the transcriptomes non-metastatic 67NR and metastatic 66cl4 cell lines from murine 4T1 mammary tumor model. The transcription factor nuclear factor, erythroid 2-like 2 (NRF2, encoded by NFE2L2) was constitutively activated cells...
Abstract Given a graph with nonnegative edge weights and set D of node pairs, the 2‐ path network problem requires minimum weight edges such that induced subgraph contains one or two connecting each pair in . The is NP ‐hard. We present integer programming models for study properties associated polytopes, including cutting planes. Two approximation algorithms are suggested analyzed. Some computational experience reported. © 2004 Wiley Periodicals, Inc.
We have previously proposed transcriptome instability as a genome-wide, pre-mRNA splicing-related characteristic of colorectal cancer. Here, we explore the hypothesis being general Exon-level microarray expression data from ten cancer datasets were analyzed, including breast cancer, cervical gastric lung neuroblastoma, and prostate (555 samples), well paired normal tissue samples colon, lung, prostate, stomach (93 samples). Based on alternative splicing scores across genomes, calculated...
Gene expression profiling has increasing relevance in the molecular screening of patients with colorectal cancer (CRC). We investigated potential platform-specific effects on transcriptomic subtyping according to established frameworks by comparisons profiles from RNA sequencing and exon-resolution microarrays 126 primary microsatellite stable CRCs. There was a strong platform correspondence global gene levels, albeit systematic technical bias likely attributed few reads covering short...
Intratubular germ cell neoplasia, the precursor of testicular tumors (TGCTs), is hypothesized to arise during embryogenesis from developmentally arrested primordial cells (PGCs) or gonocytes.In early embryonal life, PGCs migrate yolk sac dorsal body wall where population separates before colonizing genital ridges.However, whether malignant transformation takes place after this separation controversial.We have explored somatic exome-wide mutational spectra bilateral TGCT provide novel insight...
// Andreas M. Hoff 1, 2, 3, * , Bjarne Johannessen Sharmini Alagaratnam 3 Sen Zhao Torfinn Nome Marthe Løvf Anne C. Bakken Merete Hektoen Anita Sveen Ragnhild A. Lothe Rolf I. Skotheim 1 Department of Molecular Oncology, Institute for Cancer Research, Oslo University Hospital-Norwegian Radium Hospital, Oslo, Norway 2 KG Jebsen Colorectal Research Centre, Centre Biomedicine, These authors have contributed equally to this work Correspondence to: Skotheim, e-mail: rolf.i.skotheim@rr-research.no...
BACKGROUNDProstate cancer is multifocal with distinct molecular subtypes. The utility of genomic subtyping has been challenged due to inter- and intrafocal heterogeneity. We sought characterize the subtype-defining alterations primary prostate across all tumor foci within radical prostatectomy (RP) specimens determine prevalence collision tumors.METHODSFrom Early Detection Research Network cohort, we identified 333 prospectively collected RPs from 2010 2014 assessed ETS-related gene (ERG),...
Key Points Diagnostic and relapse diffuse large B-cell lymphoma (DLBCL) biopsies reveal increased mutational burden/loss of heterozygosity in HLA-A. Serially sampled tumor provide insight into therapeutic targets evolutionary divergence relapsed/refractory DLBCL.
Abstract Primary prostate cancer shows a striking intraorgan molecular heterogeneity, with multiple spatially separated malignant foci in the majority of patients. Metastatic cancer, however, typically reveals more homogenous profiles, suggesting monoclonal origin metastatic lesions. Longitudinal mutational spectra, comparing primary lesions metastases from same patients remain poorly defined. We have here analyzed somatic mutations multisampled, spatio‐temporal biobanked (38 samples and 1...
Abstract Background Colorectal cancer is the 2nd leading cause of cancer-related deaths with few patients benefiting from biomarker-guided therapy. Mutation expression essential for accurate interpretation mutations as biomarkers, but surprisingly, little has been done to analyze somatic on level. We report a large-scale analysis allele-specific mutation expression. Methods Whole-exome and total RNA sequencing was performed 137 samples 121 microsatellite stable colorectal cancers, including...
Testicular germ cell tumours (TGCTs) appear as different histological subtypes or mixtures of these. They show similar, multiple DNA copy number changes, where gain 12p is pathognomonic. However, few high-resolution analyses have been performed and focal changes with corresponding candidate target genes remain poorly described for individual subtypes. We present the first aberration (CNA) analysis on subtype embryonal carcinomas (ECs), including 13 primary ECs 5 EC lines. identified...
Dissemination within the peritoneal cavity is a main determinant of poor patient outcomes from high-grade serous carcinomas (HGSCs). The dissemination process poorly understood cancer evolutionary perspective. We reconstructed trajectories across median five tumor sites and regions each 23 patients (n=108 samples) based on deep whole-exome sequencing. Polyclonal origin was detected in one patient. Ovarian tumors had more complex subclonal architectures than other intra-peritoneal patient,...