Author: Ola Myklebost

Vokste opp på Eiksmarka og Haslum i Bærum, bodde 30 år på Trollåsen i Oppegård, bor nå på Nordnes i Bergen

Publications 2020

Akdemir KC, Le VT, Chandran S, Li Y, Verhaak RG, Beroukhim R, Campbell PJ, Chin L, Dixon JR, Futreal PA; PCAWG Structural Variation Working Group; PCAWG Consortium [Including Zaikova O, Bjerkehagen B, Myklebost O] (2020) Disruption of chromatin folding domains by somatic genomic rearrangements in human cancer. Nat Genet. 52:294-305. doi: 10.1038/s41588-019-0564-y
Alexandrov LB, Kim J, Haradhvala NJ, Huang MN, Tian Ng AW, Wu Y, Boot A, Covington KR, Gordenin DA, Bergstrom EN, Islam SMA, Lopez-Bigas N, Klimczak LJ, McPherson JR, Morganella S, Sabarinathan R, Wheeler DA, Mustonen V; PCAWG Mutational Signatures Working Group; Getz G, Rozen SG, Stratton MR; PCAWG Consortium [Including Zaikova O, Bjerkehagen B, Myklebost O] (2020) The repertoire of mutational signatures in human cancer. Nature 578:94-101. doi: 10.1038/s41586-020-1943-3

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  

Bhandari V, Li CH, Bristow RG, Boutros PC; PCAWG Consortium [Including Zaikova O, Bjerkehagen B, Myklebost O] (2020) Divergent mutational processes distinguish hypoxic and normoxic tumours. Nat Commun. 11:737. doi: 10.1038/s41467-019-14052-x

Carlevaro-Fita J, Lanzós A, Feuerbach L, Hong C, Mas-Ponte D, Pedersen JS; PCAWG Drivers and Functional Interpretation Group; Johnson R; PCAWG Consortium [Including Zaikova O, Bjerkehagen B,Myklebost O] (2020) Cancer LncRNA Census reveals evidence for deep functional conservation of long noncoding RNAs in tumorigenesis. Commun Biol. 3:56. doi: 10.1038/s42003-019-0741-7

Cmero M, Yuan K, Ong CS, Schröder J; PCAWG Evolution and Heterogeneity Working Group; Corcoran NM, Papenfuss T, Hovens CM, Markowetz F, Macintyre G; PCAWG Consortium [Including Zaikova O, Bjerkehagen B, Myklebost O] (2020) Inferring structural variant cancer cell fraction. Nat Commun. 11:730. doi: 10.1038/s41467-020-14351-8

Cortés-Ciriano I, Lee JJ, Xi R, Jain D, Jung YL, Yang L, Gordenin D, Klimczak LJ, Zhang CZ, Pellman DS; PCAWG Structural Variation Working Group; Park PJ; PCAWG Consortium [Including Zaikova O, Bjerkehagen B, Myklebost O] (2020) Comprehensive analysis of chromothripsis in 2,658 human cancers using whole-genome sequencing. Nat Genet. 52:331-341. doi: 10.1038/s41588-019-0576-7

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

Gerstung M, Jolly C, Leshchiner I, Dentro SC, Gonzalez S, Rosebrock D, Mitchell TJ, Rubanova Y, Anur P, Yu K, Tarabichi M, Deshwar A, Wintersinger J, Kleinheinz K, Vázquez-García I, Haase K, Jerman L, Sengupta S, Macintyre G, Malikic S, Donmez N, Livitz DG, Cmero M, Demeulemeester J, Schumacher S, Fan Y, Yao X, Lee J, Schlesner M, Boutros PC, Bowtell DD, Zhu H, Getz G, Imielinski M, Beroukhim R, Sahinalp SC, Ji Y, Peifer M, Markowetz F, Mustonen V, Yuan K, Wang W, Morris QD; PCAWG Evolution & Heterogeneity Working Group; Spellman PT, Wedge DC, Van Loo P; PCAWG Consortium [Including Zaikova O, Bjerkehagen B, Myklebost O] (2020) The evolutionary history of 2,658 cancers. Nature 578:122-128. doi: 10.1038/s41586-019-1907-7

Jiao W, Atwal G, Polak P, Karlic R, Cuppen E; PCAWG Tumor Subtypes and Clinical Translation Working Group; Danyi A, de Ridder J, van Herpen C, Lolkema MP, Steeghs N, Getz G, Morris QD, Stein LD; PCAWG Consortium [Including Zaikova O, Bjerkehagen B, Myklebost O] (2020) A deep learning system accurately classifies primary and metastatic cancers using passenger mutation patterns. Nat Commun.11:728. doi: 10.1038/s41467-019-13825-8

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

Li Y, Roberts ND, Wala JA, Shapira O, Schumacher SE, Kumar K, Khurana E, Waszak S, Korbel JO, Haber JE, Imielinski M; PCAWG Structural Variation Working Group; Weischenfeldt J, Beroukhim R, Campbell PJ; PCAWG Consortium [Including Zaikova O, Bjerkehagen B, Myklebost O] (2020) Patterns of somatic structural variation in human cancer genomes. Nature 578:112-121. doi: 10.1038/s41586-019-1913-9

Paczkowska M, Barenboim J, Sintupisut N, Fox NS, Zhu H, Abd-Rabbo D, Mee MW, Boutros PC; PCAWG Drivers and Functional Interpretation Working Group; Reimand J; PCAWG Consortium [Including Zaikova O, Bjerkehagen B, Myklebost O] (2020) Integrative pathway enrichment analysis of multivariate omics data. Nat Commun. 11:735. doi: 10.1038/s41467-019-13983-9

PCAWG Transcriptome Core Group; Calabrese C, Davidson NR, Demircioğlu D, Fonseca NA, He Y, Kahles A, Lehmann KV, Liu F, Shiraishi Y, Soulette CM, Urban L, Greger L, Li S, Liu D, Perry MD, Xiang Q, Zhang F, Zhang J, Bailey P, Erkek S, Hoadley KA, Hou Y, Huska MR, Kilpinen H, Korbel JO, Marin MG, Markowski J, Nandi T, Pan-Hammarström Q, Pedamallu CS, Siebert R, Stark SG, Su H, Tan P, Waszak SM, Yung C, Zhu S, Awadalla P, Creighton CJ, Meyerson M, Ouellette BFF, Wu K, Yang H; PCAWG Transcriptome Working Group; Brazma A, Brooks AN, Göke J, Rätsch G, Schwarz RF, Stegle O, Zhang Z; PCAWG Consortium [Including Zaikova O, Bjerkehagen B, Myklebost O] (2020) Genomic basis for RNA alterations in cancer. Nature 578:129-136. doi: 10.1038/s41586-020-1970-0

Reyna MA, Haan D, Paczkowska M, Verbeke LPC, Vazquez M, Kahraman A, Pulido-Tamayo S, Barenboim J, Wadi L, Dhingra P, Shrestha R, Getz G, Lawrence MS, Pedersen JS, Rubin MA, Wheeler DA, Brunak S, Izarzugaza JMG, Khurana E, Marchal K, von Mering C, Sahinalp SC, Valencia A; PCAWG Drivers and Functional Interpretation Working Group; Reimand J, Stuart JM, Raphael BJ; PCAWG Consortium [Including Zaikova O, Bjerkehagen B, Myklebost O] (2020) Pathway and network analysis of more than 2500 whole cancer genomes. Nat Commun. 11:729. doi: 10.1038/s41467-020-14367-0

Rheinbay E, Nielsen MM, Abascal F, … ; PCAWG Drivers and Functional Interpretation Working Group; PCAWG Structural Variation Working Group; Weischenfeldt J, Beroukhim R, Martincorena I, Pedersen JS, Getz G; PCAWG Consortium  [Including Zaikova O, Bjerkehagen B, Myklebost O] (2020) Analyses of non-coding somatic drivers in 2,658 cancer whole genomes. Nature 578:102-111. doi: 10.1038/s41586-020-1965-x

Rodriguez-Martin B, Alvarez EG, Baez-Ortega A, Zamora J, Supek F, …, PCAWG Structural Variation Working Group; Campbell PJ, Tubio JMC; PCAWG Consortium [Including Zaikova O, Bjerkehagen B,Myklebost O] (2020) Pan-cancer analysis of whole genomes identifies driver rearrangements promoted by LINE-1 retrotransposition. Nat Genet. 52:306-319. doi: 10.1038/s41588-019-0562-0

Rubanova Y, Shi R, Harrigan CF, Li R, Wintersinger J, Sahin N, Deshwar AG; PCAWG Evolution and Heterogeneity Working Group; Morris QD; PCAWG Consortium [Including Zaikova O, Bjerkehagen B,Myklebost O] (2020) Reconstructing evolutionary trajectories of mutation signature activities in cancer using TrackSig. Nat Commun. 11:731. doi: 10.1038/s41467-020-14352-7

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.

Shuai S; PCAWG Drivers and Functional Interpretation Working Group; Gallinger S, Stein LD; PCAWG Consortium [Including Zaikova O, Bjerkehagen B, Myklebost O] (2020) Combined burden and functional impact tests for cancer driver discovery using DriverPower. Nat Commun. 11:734. doi: 10.1038/s41467-019-13929-1 

Sieverling L, Hong C, Koser SD, Ginsbach P, Kleinheinz K, Hutter B, Braun DM, Cortés-Ciriano I, Xi R, Kabbe R, Park PJ, Eils R, Schlesner M; PCAWG-Structural Variation Working Group; Brors B, Rippe K, Jones DTW, Feuerbach L; PCAWG Consortium [Including Zaikova O, Bjerkehagen B, Myklebost O] (2020) Genomic footprints of activated telomere maintenance mechanisms in cancer. Nat Commun. 11:733. doi: 10.1038/s41467-019-13824-9

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. 

Yakneen S, Waszak SM; PCAWG Technical Working Group; Gertz M, Korbel JO; PCAWG Consortium [Including Zaikova O, Bjerkehagen B, Myklebost O] (2020) Butler enables rapid cloud-based analysis of thousands of human genomes. Nat Biotechnol. 38:288-292. doi: 10.1038/s41587-019-0360-3

Yuan Y, Ju YS, Kim Y, Li J, Wang Y, Yoon CJ, Yang Y, Martincorena I, Creighton CJ, Weinstein JN, Xu Y, Han L, Kim HL, Nakagawa H, Park K, Campbell PJ, Liang H; PCAWG Consortium [Including Zaikova O, Bjerkehagen B, Myklebost O] (2020) Comprehensive molecular characterization of mitochondrial genomes in human cancers. Nat Genet. 52:342-352. doi: 10.1038/s41588-019-0557-x

Zhang Y, Chen F, Fonseca NA, He Y, Fujita M, Nakagawa H, Zhang Z, Brazma A; PCAWG Transcriptome Working Group; PCAWG Structural Variation Working Group; Creighton CJ; PCAWG Consortium [Including Zaikova O, Bjerkehagen B, Myklebost O] (2020) High-coverage whole-genome analysis of 1220 cancers reveals hundreds of genes deregulated by rearrangement-mediated cis-regulatory alterations. Nat Commun. 11:736. doi: 10.1038/s41467-019-13885-w

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 

Løvf M, Zhao S, Axcrona U, Johannesen B, Bakken AC, Carm KT, Hoff AH, Myklebost O, Meza-Zepeda LA, Lie AK, Axcrona K, Lothe RA, Skotheim RI (2019) Multifocal Primary Prostate Cancer Exhibits High Degree of Genomic Heterogeneity. Eur Urology DOI: 10.1016/j.eururo.2018.08.009

Myklebost O (Ed) Genomsekvensering for bedre persontilpasning av kreftbehandling. (100 siders rapport fra Norsk KreftGenomikkonsortium) Jan 2019 pdf 

 

Nakken​ S, Saveliev​ V, Hofmann​ O, Møller​ P, Myklebost​ O, Hovig E Cancer Predisposition Sequencing Reporter (CPSR): a flexible variant report engine for germline screening in cancer (2019) bioRxiv preprint doi:10.1101/846089​

 

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 DOI: 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.

NoSarC, – A national, prospective sarcoma study

NoSarC, – the NOrwegian SArcoma Consortium, is a collaboration between sarcoma scientists and clinics in all Norwegian health regions to collect and analyse samples form (almost) all sarcoma patients over 3 years. Depending on funding, we are determining all mutations in the tumours by “next generation sequencing” samples from tumours and blood in all cases where tumour is available.