Publications 2021

Grad I, Hanes R, Ayuda-Durán P, Kuijjer ML, Enserink JM, Meza-Zepeda LA, Myklebost O (2021) Discovery of novel candidates for anti-liposarcoma therapies by medium-scale high-throughput drug screening. PLoS DOI:10.1371/journal.pone.0248140 

 

Peneder P, Stütz AM, Surdez D, Krumbholz M, Semper S, Chi-card M, Sheffield NC, Pierron G, Lapouble E, Tötzl M, Ergüner B, Barre-ca D, Rendeiro AF, Agaimy A, Boztug H, Engstler G, Dworzak M, Bernkopf M, Taschner-Mandl S, Ambros IM, Myklebost O, Marec-Berard P, Burchill SA, Brennan B, Strauss SJ, Whelan J, Schleiermacher G, Dirksen U, Hutter C, Boye K, Ambros PF, Delattre O, Metzler M, Bock C, Tomazou E (2021) Accurate detection and classification of Ewing sarcoma tumors based on cell-free DNA fragmentation patterns inferred from whole genome sequencing. Nature Communications In press

 

Stabell M, Sæther T, Røhr ÅK, Gabrielsen OS, Myklebost O (2021) Methylation-dependent SUMOylation of the architectural transcription factor HMGA2. Biochemical and Biophysical Research Communications, in press  

Publications 2020

Bailey MH, Meyerson WU, Dursi LJ,  ….., Gerstein MB, Ding L & PCAWG Consortium [including Bjerkehagen B, Myklebost O, Zaikova O] (2020) Retrospective evaluation of whole exome and genome mutation calls in 746 cancer samples Nature Communications volume 11, Article number: 4748 DOI: 10.1038/s41467-020-18151-y  
Dörnen J, Myklebost O, Dittmar (2020) Cell Fusion of Mesenchymal Stem/Stromal Cells and Breast Cancer Cells leads to the Formation of Hybrid Cells exhibiting diverse and individual (stem cell) Characteristics. International Journal of Molecular Sciences https://doi.org/10.3390/ijms21249636

Georgiesh T, Namløs HM, Sharma N, Lorenz S, Myklebost O, Bjerkehagen B, Meza-Zepeda LA, Boye K (2020) Clinical and molecular implications of NAB2-STAT6 fusion variants in solitary fibrous tumor Pathology doi: 10.1016/j.pathol.2020.11.010

Li CH, Prokopec SD, Sun R, Yousif F, Schmitz N, PCAWG Tumour Subtypes and Clinical Translation, Boutros PC, PCAWG Consortium (Including Bjerkehagen B, Myklebost O, Zaikova O) (2020) Sex differences in oncogenic mutational processes. Nature Communications 11:4330 DOI: 10.1038/s41467-020-17359-2

Nakken S, Saveliev V, Hofmann O, Møller P, Myklebost O, Hovig E (2020) Cancer Predisposition Sequencing Reporter (CPSR): a flexible variant report engine for high-throughput germline screening in cancer. Submitted Preprint

Namløs H, Skårn M, Ahmed D, Grad I, Andresen K, Kresse S, Serra M, Scotlandi K, Llombart-Bosch A, Myklebost O, Lind G, Meza-Zepeda LA (2920) miR-486 expression is regulated by DNA methylation in osteosarcoma Submitted Preprint

Serguienko A, Braadland P, Meza-Zepeda LA, Bjerkehagen B, Myklebost O (2020) Accurate 3-gene-signature for early diagnosis of liposarcoma progression. Clinical Sarcoma Research 10:4 DOI: 10.1186/s13569-020-0126-1.

The ICGC/TCGA Pan-Cancer Analysis of Whole Genomes Consortium [Incl Bjerkehagen B, Myklebost O, Zaikova O] (2020) Pan-cancer analysis of whole genomes. Nature 578:82–93 doi:10.1038/s41586-020-1969-6 

Wise JF, Nakken S, Steen CB, Vodák D, Trøen G, Johannessen B, Lingjærde OC, Hilden V, Blaker YN, Bai B, Aasheim LB, Pasanen A, Lorenz S, Sveen A, Lothe RA, Myklebost O, Leppä S, Meza-Zepeda LA, Beiske K, Lawrence MS, Hovig E, Myklebust JH, Smeland EB, Holte H (2020) Mutational Dynamics and Immune Evasion in Diffuse Large B-cell Lymphoma: A Call for Relapse Sampling Blood Adv 12;4(9):1859-1866. doi: 10.1182/bloodadvances.2019001325. 

Publications 2019

Hanes R, Munthe E, Grad I, Han J, Karlsen I, McCormack E, Meza-Zepeda LA, Stratford EW, Myklebost O (2019) Preclinical evaluation of the pan-FGFR inhibitor LY2874455 in FRS2-amplified liposarcoma. Special Issue “Fibroblast Growth Factor Receptor (FGFR) Signaling Pathway in Tumor: Cells 2019, 8(2), 189; PDF (Open Access) DOI:10.3390/cells8020189  

Myklebost O (Ed) Genomsekvensering for bedre persontilpasning av kreftbehandling. (100 p report from the Cancer Genomics Consortium in Norwegian) Jan 2019 pdf 

Publications 2018

Birkeland E, Zhang S, Poduval D, Geisler J, Nakken S, Vodak D, Meza-Zepeda LA, Hovig E, Myklebost O,Knappskog S, Lønning PE (2018) Patterns of genomic evolution in advanced melanoma. Nature Comm DOI: 10.1038/s41467-018-05063-1  

Gouravan S, Meza-Zepeda LA, Myklebost O, Stratford EW, Munthe E (2018) Preclinical evaluation of vemurafenib as therapy for BRAFV600E mutated sarcomas Int J Mol Sci DOI:10.3390/ijms19040969 

Kresse SK, Namløs HM, Lorenz S, Berner JM, Ola Myklebost O, Bjerkehagen B, Meza-Zepeda LA(2018) Evaluation of commercial DNA and RNA extraction methods for high-throughput sequencing of FFPE samples. PLoS One https://doi.org/10.1371/journal.pone.0197456 

Nakken S, Fournous G, Vodak D, Aasheim B, Myklebost O, Hovig E (2017) Personal Cancer Genome Reporter: Variant Interpretation Report For Precision Oncology. Bioinformatics 1–3 doi:10.1093/bioinformatics/btx817 

Namløs H, Boye K, Mishkin SJ, Barøy T, Lorenz S, Bjerkehagen B, Stratford EW, Munthe E, Kudlow BA, Myklebost O, Meza-Zepeda LA(2018) Non-invasive detection of ctDNA reveals intratumour heterogeneity and is significantly associated with aggressive GIST Mol Cancer Ther  10.1158/1535-7163.MCT-18-0174

Serguienko A, Wang MY, Myklebost O(2018) Real-time vital mineralization detection and quantification during in vitro osteoblast differentiation. Biological Procedures Online (2018) 20:14 DOI: 10.1186/s12575-018-0079-4 

Strauss SJ, Anninga J, Baglio B, Baumhoer D, Behjati S, Bielack S, Boye K, Broto JM, Cleton‑Jansen AM, Degasperi A, Evans A, Fagioli F, Fiocco M, Gaspar N, Heymann D, Hindi N, Lancia C, Myklebost O, Nathrath M, Redini F, Scotlandi K, Tirtei E, Vanden Eynden M, Whelan J (2018) Report from the 4th European Bone Sarcoma Networking meeting: focus on osteosarcoma Clin Sarcoma Res 8:17 DOI:10.1186/s13569-018-0103-0 

Vodák D, Lorenz S, Nakken S, Aasheim LB, Holte H, Bai B, Myklebost O, Meza-Zepeda LA, Hovig E (2018) Sample-Index Misassignment Impacts Tumour Exome Sequencing Sci. Rep. DOI:10.1038/s41598-018-23563-4 

 

Repurposing drugs for sarcoma patients

Like so many orphan, or neglected, cancers, therapies for sarcomas have, with a few exceptions, not improved much the last decades. Surgery, radiation and chemotherapy are the main treatment arms, but chemotherapy appears to have reached a limit due to high toxicities, and has not significantly improved this century. A notable exception is the treatment of GIST with drugs targeting the c-kit pathway, which is a prime example of successful repurposing of a drug. Imatinib was developed to target the fusion protein bcr-abl which causes leukemia, but turned out to also be very effective against the mutated kit receptor in GIST (gastrointestinal stromal tumours). We are trying to identify other such drugs, developed and perhaps approved for another cancer type, but having activity against sarcomas.

Candidate sarcoma drugs are identified by two main projects: Determining cancer mechanisms that are mutated in sarcomas, or drug screening of drug libraries on sarcoma cells in culture. In the first project we identify mutated mechanisms that have been exploited in therapies in other cancers. However, although we may find the same mutations that predict response in another cancer, this may not be the case in sarcomas. We therefore have to find one or more cell lines with this type of mutation, and test their sensitivity to the drug. If it works it is promising, but we still do not know if it will work in a patient, as there are so many differences between a cell culture and a body. Some of these issues may be accounted for by investigating the activity in a human sarcoma grown in mice, but still this is just a first stepping-stone for clinical trials, there are many differences between such an artificial experimental system and real tumours in patients.

To determine the efficacy in patients, a clinical trial has to be organised and funded.