title: Whole exome sequencing of a single osteosarcoma case--integrative analysis with whole transcriptome RNA-seq data.
abstract: BACKGROUND
  Osteosarcoma (OS) is a prevalent primary malignant bone tumour with unknown etiology. These highly metastasizing tumours are among the most frequent causes of cancer-related deaths. Thus, there is an urgent need for different markers, and with our study, we were aiming towards finding novel biomarkers for OS.
  
  
  METHODS
  For that, we analysed the whole exome of the tumorous and non-tumour bone tissue from the same patient with OS applying next-generation sequencing. For data analysis, we used several softwares and combined the exome data with RNA-seq data from our previous study.
  
  
  RESULTS
  In the tumour exome, we found wide genomic rearrangements, which should qualify as chromotripsis-we detected almost 3,000 somatic single nucleotide variants (SNVs) and small indels and more than 2,000 copy number variants (CNVs) in different chromosomes. Furthermore, the somatic changes seem to be associated to bone tumours, whereas germline mutations to cancer in general. We confirmed the previous findings that the most significant pathway involved in OS pathogenesis is probably the WNT/β-catenin signalling pathway. Also, the IGF1/IGF2 and IGF1R homodimer signalling and TP53 (including downstream tumour suppressor gene EI24) pathways may have a role. Additionally, the mucin family genes, especially MUC4 and cell cycle controlling gene CDC27 may be considered as potential biomarkers for OS.
  
  
  CONCLUSIONS
  The genes, in which the mutations were detected, may be considered as targets for finding biomarkers for OS. As the study is based on a single case and only DNA and RNA analysis, further confirmative studies are required.
authors.affiliation: Department of Pathophysiology, University of Tartu, 19 Ravila Street, Tartu, 50411, Estonia. ene.reimann@ut.ee.|Department of Reproductive Biology, Estonian University of Life Sciences, 64 Kreutzwaldi Street, Tartu, Estonia. ene.reimann@ut.ee.
authors.forename: Ene
authors.initials: E
authors.lastname: Reimann
authors.affiliation: Department of Pathophysiology, University of Tartu, 19 Ravila Street, Tartu, 50411, Estonia. sulev.koks@ut.ee.|Department of Reproductive Biology, Estonian University of Life Sciences, 64 Kreutzwaldi Street, Tartu, Estonia. sulev.koks@ut.ee.
authors.forename: Sulev
authors.initials: S
authors.lastname: Kõks
authors.affiliation: Department of Traumatology and Orthopaedics, University of Tartu, 8 Puusepa Street, Tartu, Estonia. xuandung59@gmail.com.|Department of Oncology, Hue University of Medicine and Pharmacy, 6 Ngo Quyen Street, Hue, Vietnam. xuandung59@gmail.com.
authors.forename: Xuan Dung
authors.initials: XD
authors.lastname: Ho
authors.affiliation: Department of Traumatology and Orthopaedics, University of Tartu, 8 Puusepa Street, Tartu, Estonia. katre.maasalu@kliinikum.ee.|Traumatology and Orthopaedics Clinic, Tartu University Hospital, 8 Puusepa Street, Tartu, Estonia. katre.maasalu@kliinikum.ee.
authors.forename: Katre
authors.initials: K
authors.lastname: Maasalu
authors.affiliation: Department of Traumatology and Orthopaedics, University of Tartu, 8 Puusepa Street, Tartu, Estonia. aare.martson@kliinikum.ee.|Traumatology and Orthopaedics Clinic, Tartu University Hospital, 8 Puusepa Street, Tartu, Estonia. aare.martson@kliinikum.ee.
authors.forename: Aare
authors.initials: A
authors.lastname: Märtson
mesh_terms: D000293:Adolescent; D064191:Apc3 Subunit, Anaphase-Promoting Complex-Cyclosome / Q000235:genetics; D051017:Apoptosis Regulatory Proteins / Q000235:genetics; D002888:Chromosomes, Human, Pair 19 / Q000235:genetics; D002889:Chromosomes, Human, Pair 2 / Q000235:genetics; D019295:Computational Biology; D056915:DNA Copy Number Variations; D059472:Exome; D015972:Gene Expression Regulation, Neoplastic; D005819:Genetic Markers; D018095:Germ-Line Mutation; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000235:genetics; D007335:Insulin-Like Growth Factor II / Q000235:genetics; D008297:Male; D055264:Mucin-4 / Q000235:genetics; D009687:Nuclear Proteins / Q000235:genetics; D012516:Osteosarcoma / Q000175:diagnosis / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D017526:Receptor, IGF Type 1; D017451:Receptors, Somatomedin / Q000235:genetics; D017423:Sequence Analysis, RNA; D015398:Signal Transduction; D012984:Software; D059467:Transcriptome; D016159:Tumor Suppressor Protein p53 / Q000235:genetics; D044465:White People / Q000235:genetics; D051176:beta Catenin / Q000235:genetics
chemical_list: D064191:Apc3 Subunit, Anaphase-Promoting Complex-Cyclosome; D051017:Apoptosis Regulatory Proteins; C577366:CDC27 protein, human; C402592:EI24 protein, human; D005819:Genetic Markers; C583557:IGF1 protein, human; C000597236:IGF1R protein, human; C035170:IGF2 protein, human; C524658:MUC4 protein, human; D055264:Mucin-4; D009687:Nuclear Proteins; D017451:Receptors, Somatomedin; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D051176:beta Catenin; D007334:Insulin-Like Growth Factor I; D007335:Insulin-Like Growth Factor II; D017526:Receptor, IGF Type 1