Biology subjects

Russnes, H. G.

Publications and source records attributed to Russnes, H. G..

4 recordsLinked to original sources

bioRxiv2026

CANCAN: high-resolution copy number and mutation heterogeneity analysis of DNA sequence data for clinical applications

High-throughput DNA sequencing is central to precision oncology, yet robust and interpretable methods for integrated analysis of copy number alterations and somatic variants across sequencing platforms remain limited. We present CANCAN (Copy number integrative ANalysis in CANcer), a platform-agnostic computational framework for high-resolution analysis of allele-specific copy number and variant data. CANCAN integrates novel normalization and segmentation strategies and enables inference of tumor purity, ploidy, subclonality and mutation multiplicity, while providing statistical confidence estimates and transparent evaluation of alternative solutions. Benchmarking across whole-genome, whole-exome and targeted sequencing datasets from TCGA and the IMPRESS-Norway study demonstrates high concordance with established methods, with particularly strong performance on targeted sequencing data. CANCAN accurately estimates global genomic features, including purity and ploidy, even at reduced sequencing coverage, and shows comparable or improved agreement relative to existing tools. In addition, it provides detailed visualization of the genomic context of clinically relevant biomarkers, supporting diagnostic interpretation. CANCAN constitutes a reproducible and interpretable approach for integrated genomic analysis, addressing key methodological and practical challenges in clinical cancer genomics.

bioinformatics↗

bioRxiv2020

NG2+/Nestin+ mesenchymal stem cells dictate DTC dormancy in the bone marrow through TGFβ2

In the bone marrow (BM) microenvironment, NG2+/Nestin+ mesenchymal stem cells (MSCs) promote hematopoietic stem cell (HSC) quiescence1,2. Importantly, the BM can also harbour disseminated tumour cells (DTCs) from multiple cancers, which, like HSCs, can remain dormant3. The BM signals are so growth-restrictive that dormant BM DTCs can persist for years to decades only to awaken and fuel lethal metastasis3-10. The mechanisms and niche components regulating DTC dormancy remain largely unknown. Here, we reveal that periarteriolar BM-resident NG2+/Nestin+ MSCs can instruct breast cancer (BC) DTCs to enter dormancy. NG2+/Nestin+ MSCs produce TGF{beta}2 and BMP7 and activate a quiescence pathway dependent on TGFBRIII and BMPRII, which via p38-kinase result in p27-CDK inhibitor induction. Importantly, genetic depletion of the NG2+/Nestin+ MSCs or conditional knock-out of TGF{beta}2 in the NG2+/Nestin+ MSCs led to awakening and bone metastatic expansion of otherwise dormant p27+/Ki67- DTCs. Our results provide a direct proof that HSC dormancy niches control BC DTC dormancy. Given that aged NG2+/Nestin+ MSCs can lose homeostatic control of HSC dormancy, our results suggest that aging or extrinsic factors that affect the NG2+/Nestin+ MSC niche may result in a break from dormancy and BC bone relapse.

cancer biology↗

bioRxiv2019

Copy number motifs expose genome instability type and predict driver events and disease outcome in breast cancer

Tumor evolution is dependent on and constrained by the genotypes emerging from genome instability. We hypothesized that non-site-specific copy number motifs would correlate with underlying replication defects and also with tumor and patient fate. Six feature detectors were defined to characterize and score the local spatial behaviour of a copy number profile. By accumulating scores across genomic regions, a low-dimensional representation of the tumor genome was obtained. The proposed Copy Aberration Regional Mapping Analysis (CARMA) algorithm was applied to 2384 breast tumors from three breast cancer cohorts, revealing distinct copy number motifs in established molecular subtypes. A prognostic index combining the features predicted breast cancer specific survival better than both the genomic instability index (GII) and all commonly used clinical stratifications. CARMA offers effective comparison of tumor subgroups and extracts biologically and clinically relevant features from allele-specific copy number profiles.

bioinformatics↗

bioRxiv2018

Intra-tumor heterogeneity defines treatment-resistant HER2+ breast tumors

Targeted therapy for patients with HER2 positive (HER2+) breast cancer has improved the overall survival, but many patients still suffer relapse and death of the disease. Intra-tumor heterogeneity of both estrogen receptor (ER) and HER2 expression has been proposed to play a key role in treatment failure, but little work has been done to comprehensively study this heterogeneity at the single-cell level.\n\nIn this study, we explored the clinical impact of intra-tumor heterogeneity of ER protein expression, HER2 protein expression, and HER2 gene copy number alterations. Using combined immunofluorescence and in situ hybridization on tissue sections followed by a validated computational approach, we analyzed more than 13,000 single tumor cells across 37 HER2+ breast tumors. The samples were taken both before and after neoadjuvant chemotherapy plus HER2-targeted treatment, enabling us to study tumor evolution as well.\n\nWe found that intra-tumor heterogeneity for HER2 copy number varied substantially between patient samples. Highly heterogeneous tumors were associated with significantly shorter disease-free survival and fewer long-term survivors. Patients for which HER2 characteristics did not change during treatment had a significantly worse outcome.\n\nThis work shows the impact of intra-tumor heterogeneity in molecular diagnostics for treatment selection in HER2+ breast cancer patients and the power of computational scoring methods to evaluate in situ molecular markers in tissue biopsies.

cancer biology↗