A5069373137- Colorectal Cancer Treatments and Studies
- Cancer Genomics and Diagnostics
- Genetic factors in colorectal cancer
- Cancer, Hypoxia, and Metabolism
- Pharmacogenetics and Drug Metabolism
- Computational Drug Discovery Methods
- RNA modifications and cancer
- Cancer-related molecular mechanisms research
- Neuroblastoma Research and Treatments
- Neurofibromatosis and Schwannoma Cases
- Lung Cancer Treatments and Mutations
- Nutrition, Genetics, and Disease
- Sarcoma Diagnosis and Treatment
- Hepatocellular Carcinoma Treatment and Prognosis
- Mycobacterium research and diagnosis
- Chemical Reactions and Isotopes
- Radiomics and Machine Learning in Medical Imaging
- Cancer, Lipids, and Metabolism
- Ferroptosis and cancer prognosis
- Genomic variations and chromosomal abnormalities
- Immune cells in cancer
- Cancer Mechanisms and Therapy
- PARP inhibition in cancer therapy
- RNA regulation and disease
- Colorectal Cancer Screening and Detection
Oslo University Hospital
2012-2024
Molecular Oncology (United States)
2018-2023
University of Oslo
2012-2023
ORCID
2023
Universitair Ziekenhuis Leuven
2023
Norwegian Cancer Society
2017-2023
Cancer Registry of Norway
2016
Cell lines are invaluable biomedical research tools, and recent literature has emphasized the importance of genotype authentication characterization. In present study, 24 out 27 cell line identities were confirmed by short tandem repeat profiling. The molecular phenotypes colon cancer examined, microsatellite instability (MSI) CpG island methylator phenotype (CIMP) determined, using Bethesda panel mononucleotide loci two epimarker panels, respectively. Furthermore, BRAF, KRAS PIK3CA...
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...
Purpose: Response to standard oncologic treatment is limited in colorectal cancer. The gene expression-based consensus molecular subtypes (CMS) provide a new paradigm for stratified and drug repurposing; however, discovery currently by the lack of translation CMS preclinical models.Experimental Design: We analyzed primary cancers, cell lines, patient-derived xenografts (PDX). For classification models, we developed an optimized classifier enriched cancer cell-intrinsic expression signals,...
Abstract Purpose: Molecular tumor heterogeneity may have important implications for the efficacy of targeted therapies in metastatic cancers. Inter-metastatic sensitivity to anticancer agents has not been well explored colorectal cancer. Experimental Design: We established a platform ex vivo pharmacogenomic profiling patient-derived organoids (PDO) from resected cancer liver metastases. Drug testing (n = 40 clinically relevant agents) and gene expression were performed on 39 metastases 22...
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.
We have previously shown that gastrointestinal cancers display similar epigenetic aberrations. In a recent study, we identified frequently methylated genes for cholangiocarcinoma (CDO1, DCLK1, SFRP1 and ZSCAN18), where one of these genes, was also confirmed to be highly in colorectal cancer. The aim the present study determine whether four addition gene found colon cancer cell lines (ZNF331), are commonly across malignancies, as well explore their role potential biomarkers. Quantitative...
BackgroundThe prognostic impact of KRAS and BRAFV600E mutations in primary colorectal cancer (CRC) varies with microsatellite instability (MSI) status. The gene expression–based consensus molecular subtypes (CMSs) CRC define molecularly clinically distinct subgroups, represent a novel stratification framework biomarker analysis. We investigated the value these within CMS groups.Patients methodsTotally 1197 tumors from Norwegian series stage I–IV were analyzed for MSI mutation status hotspots...
Abstract Gene expression-based subtypes of colorectal cancer have clinical relevance, but the representativeness primary tumors and consensus molecular (CMS) for metastatic cancers is not well known. We investigated heterogeneity CMS. The best approach to subtype translation was delineated by comparisons transcriptomic profiles from 317 295 liver metastases, including multi-metastatic samples 45 patients 14 primary-metastasis sets. Associations were validated in an external data set ( n =...
Tumor-associated macrophages (TAMs) are associated with unfavorable patient prognosis in many cancer types. However, TAMs a heterogeneous cell population and subsets have been shown to activate tumor-infiltrating T cells confer good prognosis. Data on the prognostic value of colorectal conflicting. We investigated effect relation cancers.
We aimed to refine the value of CDX 2 as an independent prognostic and predictive biomarker in colorectal cancer ( CRC ) according disease stage chemotherapy sensitivity preclinical models. expression was evaluated 1045 I– IV primary s by gene n = 403) or immunohistochemistry 642) relation 5‐year relapse‐free survival RFS ), overall OS chemotherapy. Pharmacogenomic associations between 69 chemotherapeutics were assessed drug screening 35 cell lines. lost 11.6% cases showed poor multivariable...
Abstract The BRAFV600E mutation, present in 8 - 10% of colorectal cancers (CRCs), is associated with poor patient outcome and has limited treatment options. Recent studies have shown that mutations the E3 ubiquitin ligase RNF43 predict response to anti-EGFR/BRAF combinatory therapy patients metastatic CRC. Gene expression analysis CRCs BRAF/RNF43 co-mutation exhibit significantly higher levels MAP2K1 MAPK3 compared their wild-type counterparts. This implies an unknown but clinically...
Elevated miR-31 expression is associated with poor outcome in colorectal cancer (CRC). Whether the prognostic information independent of known molecular subgroups and gene expression-based consensus subtypes (CMS) currently unknown. To investigate this, we analyzed nearly 2000 CRC biopsies preclinical models. The miR-31-5p its host transcript, long noncoding RNA MIR31HG, was strongly correlated (Spearman's ρ > 0.80). MIR31HG outlier observed 158/1265 (12%) pCRCs depletion CMS2-canonical...
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....
Intra-tumor heterogeneity compromises the clinical value of transcriptomic classifications colorectal cancer. We investigated prognostic effect and potential for less vulnerable to in a single-hospital series 1093 tumor samples from 692 patients, including multiregional 98 primary tumors 35 primary-metastasis sets. show that intra-tumor consensus molecular subtypes (CMS) is frequent has poor-prognostic associations independently microenvironment markers. Multiregional transcriptomics uncover...
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...
KRAS mutation is a well-known marker for poor response to targeted treatment and patient prognosis in microsatellite stable (MSS) colorectal cancer (CRC). However, variation clinical outcomes among patients wild-type underlines that this not homogeneous population. Here, we evaluated the prognostic impact of alternative splicing relation status single-hospital series primary MSS CRCs (N = 258). Using splicing-sensitive microarrays RNA sequencing, relative expression KRAS-4A versus KRAS-4B...
Abstract Background Gene expression-based subtyping has the potential to form a new paradigm for stratified treatment of colorectal cancer. However, current frameworks are based on transcriptomic profiles primary tumors, and metastatic heterogeneity is challenge. Here we aimed develop de novo metastasis-oriented framework. Methods In total, 829 from patients with cancer were analyzed, including liver metastases, non-malignant samples. High-resolution microarray gene expression profiling was...
Patients with malignant peripheral nerve sheath tumor ( MPNST ), a rare soft tissue cancer associated loss of the suppressor neurofibromin NF 1), have poor prognosis and typically respond poorly to adjuvant therapy. We evaluated effect 299 clinical investigational compounds on seven cell lines, two primary cultures human Schwann cells, five normal bone marrow aspirates, identify potent drugs for treatment few side effects. Top hits included Polo‐like kinase 1 PLK 1) inhibitors (volasertib BI...
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...
Accumulating evidence suggests immunomodulatory and context-dependent effects of