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.

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.

Publications 2017

Behjati S, Tarpey PS, Haase K, Ye H, Young MD, Alexandrov LB, Farndon SJ, Collord G, Wedge DC, Martincorena I, Cooke SL, Davies H, Mifsud W, Lidgren M, Martin S, Latimer C, Maddison M, Butler AP, Teague JW, Pillay N, Shlien A, McDermott U, Futreal PA, Baumhoer D, Zaikova O, Bjerkehagen B, Myklebost O, Amary MF, Tirabosco R, Van Loo P, Stratton MR, Flanagan AM, Campbell PJ (2017) Recurrent mutation of IGF signalling genes and distinct patterns of genomic rearrangement in osteosarcoma Nature Communications 23:15936 doi: 10.1038/ncomms15936

Berg KCG, Eide PW, Eilertsen IA, Johannessen B, Bruun J, Danielsen SA, Bjørnslett M, Meza-Zepeda LA, Eknæs M, Lind GE, Myklebost O, Skotheim RI, Sveen A, Lothe RA (2017) Multi-omics of 34 colorectal cancer cell lines – a resource for biomedical studies Mol Cancer 16:116 doi: 10.1186/s12943-017-0691-y

Engkvist ME, Stratford EW, Lorenz S, Meza-Zepeda LA, Munthe E, Myklebost O (2017) Analysis of the miR-34 family functions in breast cancer reveals annotation error of miR-34b Sci Rep DOI:10.1038/s41598-017-10189-1

Helland Å, Brustugun OT, Nakken S, Halvorsen AR, Dønnem T, Bremnes R, Busund LT, Sun J, Lorenz S, Solberg SK, Jørgensen LH, Vodak D, Myklebost O, Hovig E, Meza-Zepeda LA (2017) High number of kinome-mutations in non-small cell lung cancer is associated with reduced immune response and poor relapse-free survival. Int J Cancer 141:184-190 doi: 10.1002/ijc.30726

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

Rustad EH, Coward E, Skytøen ER, Misund K, Holien T, Standal T, Børset M, Beisvag V, Myklebost O, Meza-Zepeda LA, Dai HY, Sundan A, Waage A (2017) Monitoring of Multiple Myeloma by quantification of recurrent mutations in serum Haematologica 102:1266-1272 doi: 10.3324/haematol.2016.160564

Serguienko A, Hanes R,Grad I, Wang MY, Munthe E, Myklebost O (2017) PP2A regulatory subunit B55γ is a gatekeeper of osteoblast maturation and lineage maintenance Stem Cells Devel 26: 1375-1383 doi: 10.1089/scd.2017.0129

Sveen A, Johannessen B, Tengs T, Danielsen SA, Eilertsen IA, Lind GE, Berg KCG, Leithe E, Meza-Zepeda LA, Domingo E, Myklebost O, Kerr D, Tomlinson I, Nesbakken A, Skotheim RI, Lothe RA (2017) Multilevel genomics of colorectal cancers with microsatellite instability – clinical impact of JAK1 mutations and consensus molecular subtype 1 Genome Medicine 9:46 doi: 10.1186/s13073-017-0434-0

Publications 2016

Ballinger ML, Goode DL, Ray-Coquard I, James PA, Mitchell G, Niedermayr E, Puri A, Schiffman JD, Dite GS, Cipponi A, Maki RG, Brohl AS, Myklebost O, Stratford EW, Lorenz S, Ahn SM, Ahn JH, Kim JE, Shanley S, Beshay V, Randall L, Judson I, Seddon B, Cambell IG, Young MA, Sarin R, Blay JY, O’Donoghue SI, Thomas D (2016Novel monogenic and polygenic determinants of sarcoma risk: an international study of 1162 families Lancet Oncology 17:1261–1271 PDF

Barøy T, Chilamakuri CSR, Lorenz S, Sun J, Bruland ØS, Myklebost O, Meza-Zepeda LA (2016) Genome analysis of osteosarcoma progression samples identifies FGFR1 overexpression as a potential treatment target and CHM as a candidate tumor suppressor gene Plos One 11: e0163859 DOI:10.1371/journal.pone.0163859

Halvorsen AR, Silwal-Pandit L, Meza-Zepeda LA, Vodak D, Vu P, Sagerup C, Hovig E, Myklebost O; Børresen-Dale AL, Brustugun OT, Helland Å (2016) TP53 mutation spectrum in smokers and never smoking lung cancer patients Frontiers in Genetics 7:85.

Hanes, R., I. Grad, S. Lorenz, E. W. Stratford, E. Munthe, C. C. S. Reddy, L. A. Meza-Zepeda and O. Myklebost(2016). Amplified FRS2 identified as a target for treatment of dedifferentiated liposarcoma by genome sequencing and functional validation. Oncotarget 7:54583.

Kager L, Whelan J, Dirksen U, Hassan B, Anninga J, Bennister L, Bovée JV, Brennan B, Broto JM, Brugières L, Cleton-Jansen AM, Copland C, Dutour A, Fagioli F, Ferrari S, Fiocco M, Fleuren E, Gaspar N, Gelderblom H, Gerrand C, Gerß J, Gonzato O, van der Graaf W, Hecker-Nolting S, Herrero-Martín D, Klco-Brosius S, Kovar H, Ladenstein R, Lancia C, LeDeley MC, McCabe MG, Metzler M, Myklebost O, Nathrath M, Picci P, Potratz J, Redini F, Richter GH, Reinke D, Rutkowski P, Scotlandi K, Strauss S, Thomas D, Tirado OM, Tirode F, Vassal G, Bielack SS (2016) The ENCCA-WP7/EuroSarc/EEC/PROVABES/EURAMOS 3rd European Bone Sarcoma Networking Meeting/Joint Workshop of EU Bone Sarcoma Translational Research Networks; Vienna, Austria, September 24-25, 2015. Workshop Report. Clin Sarcoma Res. 16;6:3

Namløs HM, Zaikova O, Bjerkehagen B, Vodák D, Hovig E, Myklebost O, Boye K, Meza-Zepeda LA (2016) Use of liquid biopsies to monitor disease progression in a sarcoma patient: a case report BMC Cancer In press

Sandhu V, Wedge DC, Lothe IMB, Labori KJ, Dentro SC, Buanes T, Skrede ML, Dalsgaard AM, Munthe E, Myklebost O, Lingjærde OC, Børressen-Dale AL, Ikdahl T, Van Loo P, Nord S (2016) The genomic landscape of pancreatic and periampullary adenocarcinoma. Cancer Research 76(17); 1–11

Våtsveen TK, Børset M, Dikic A, Tian E, Micci F, Lid AH, Meza-Zepeda LA, Coward E, Waage A, Sundan A, Kuehl WM, Holien T (2016)
VOLIN and KJON-Two novel hyperdiploid myeloma cell lines Genes Chromosomes Cancer, 55 (11), 890-901
PubMed 27311012

Publications 2015

Budin-Ljøsne I, Bentzen HB, Solbakk JH, Myklebost O (2015) Genome sequencing in research requires a new approach to consent Tidskr Nor Legeforening PDF

Chymkowitch P, Nguéa P A, Aanes H, Koehler CJ, Thiede B, Lorenz S, Meza-Zepeda LA, Klungland A, Enserink JM (2015) Sumoylation of Rap1 mediates the recruitment of TFIID to promote transcription of ribosomal protein genes Genome Res, 25 (6), 897-906 PubMed 25800674

Fernandez-Cuesta L, Sun R, Menon R, George J, Lorenz S, Meza-Zepeda LA, Peifer M, Plenker D, Heuckmann JM, Leenders F, Zander T, Dahmen I, Koker M, Schöttle J, Ullrich RT, Altmüller J, Becker C, Nürnberg P, Seidel H, Böhm D, Göke F, Ansén S, Russell PA, Wright GM, Wainer Z et al. (2015) Identification of novel fusion genes in lung cancer using breakpoint assembly of transcriptome sequencing data. Genome Biol, 16, 7 PubMed 25650807

Ju YS, Tubio JMC, Mifsud W, Fu B, Davies HR, Ramakrishna M, Li Y, Yates L, Gundem G, Tarpey PS, Behjati S, Papaemmanuil E, Martin S, Fullam A,Gerstung M, ICGC Prostate Cancer Working Group, ICGC Bone Cancer Working Group, ICGC Breast Cancer Working Group, Nangalia J, Green AR, Caldas C, Borg Å, Tutt A, Ta M, Lee M, van’t Veer LJ, Tan BKT, Aparicio S, Span PN, Martens JWM, Knappskog S, Vincent-Salomon A, Børresen-Dale AL, Eyfjörd JE, Myklebost O, Flanagan AM, Foster C, Neal DE, Cooper C, Eeles R, Lakhani SR, Desmedt C, Thomas G, Richardson AL, Purdie CA, Thompson AM, McDermott U, Yang F, Nik-Zainal S, Campbell PM, Stratton MR (2015) Frequent somatic transfer of mitochondrial DNA into the nuclear genome of human cancer cells Genome Res 25:814-24. doi: 10.1101/gr.190470.115

Kanojia D, Nagata Y, Garg M, Lee DH, Anand MT, Christoph H, Klein HU, Said JW, Doan NB, Mohith S, Gunasekar S, Myklebost O, Yang H, Dugas M, Meza‐Zepeda LA, Silberman AW, Forscher C, Ogawa S, Koeffler HP (2015) Genomic landscape of liposarcoma Oncotarget DOI: 10.18632/oncotarget.6464

Lorenz S, Barøy T, Sun J, Nome T, Vodák D, Bryne JC, Håkelien AM, Fernandez-Cuesta L, Möhlendick B, Rieder H, Szuhai K, Zaikova O, Ahlquist TC, Thomassen GOS, Skotheim RI, Lothe RA, Tarpey P, Campbell P, Flanagan A, Meza-Zepeda LA, Myklebost O (2015) Unscrambling the genomic chaos of osteosarcoma reveals recurrent rearrangements and frequent novel TP53 aberrations Oncotarget DOI: 10.18632/oncotarget.6567

Myklebost O (2015) Personalized cancer therapy for soft tissue sarcomas: progress and pitfalls (Review) Personalized Medicine 12:593-602 PDF

Myklebost O (2015) Norwegian Cancer Genomics Consortium, a platform for research on personalized cancer medicine in a public health system. Drug Discovery Today: Special issue on Stratified Medicine doi:10.1016/j.drudis.2015.10.003

Naderi EH, Ugland H, Myklebost O, Sandnes DL, Torgersen ML, Josefsen D, Ellen Ruud E, Naderi S, Blomhoff HK (2015) Bone marrow stroma-derived PGE2 protects BCP-ALL cells from DNA damage-induced p53 accumulation and cell death, Mol Cancer in press doi:10.1186/s12943-014-0278-9

Rustad EH, Dai HY, Hov H, Coward E, Beisvag V, Myklebost, Ola, Nakken S, Vodak D, Meza-Zepeda LA, Hovig E,Sandvik A, Wader KF, Misund K, Sundan A, Aarset H, Waage A (2015) Clinical and biological implications of BRAF V600E mutation in multiple myeloma. Blood Cancer J doi:  10.1038/bcj.2015.24

Safavi S, Järnum S, Vannas C, Udane S, Jonasson E, Tomic TT, Grundevik P, Fagman H, Hansson M, Kalender Z, Jauhiainen A, Dolatabadi S, Stratford EW, Myklebost O, Eriksson M, Stock ES, Ståhlberg A, Åman P (2015) HSP90 inhibition blocks ERBB3 and RET phosphorylation in myxoid/round cell liposarcoma and causes massive cell death in vitro and in vivo. Oncotarget  PDF

Serguienko A, Grad I, Wennerstrøm AB, Meza-Zepeda LA, Thiede B, Stratford EW, Ola Myklebost O, Munthe E (2015) Metabolic reprogramming of metastatic breast cancer and melanoma by let-7a microRNA Oncotarget 6(4): 2451–2465