Cytogenetic and Molecular Cytogenetic Analyses of Brain Tumours
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- Institutt for klinisk medisin [10950]
Sammendrag
Cancer is the phenotypic result of susceptible somatic target cells acquiring one or more oncogenic chromosomal and/or gene-level mutations. Screening the whole tumour genome is therefore a natural starting point when trying to understand the pathogenetic mechanisms behind tumour development. Gliomas and paediatric embryonal tumours are challenging neoplasms both diagnostically and therapeutically. Overlapping histopathological features results in high interobserver variability when they are diagnosed phenotypically and there is a call for an alternative grouping of tumours that could hopefully provide information about prognosis as well as key insights into molecular disease mechanisms that may eventually be translated into more effective and individualised therapies. The overall aim of this thesis was to characterise brain tumours by genome-wide as well as more specific molecular cytogenetic techniques. As each cytogenetic technique has its strengths and limitations, there is a clear need for a multi-modal approach when analysing tumour genomes. Our multi-modal approach involved analysis of chromosomes from brain tumour cells by various combinations of G-banding, comparative genomic hybridisation (CGH) (chromosomal and array-based), multiplex FISH (M-FISH), and, in some instances, locus-specific FISH and DNA ploidy analysis. This combined approach identified a non-random pattern of genomic aberrations in all the examined disease entities. This may prove to be of diagnostic value as well as help identify genomic subsets of patients with high-risk disease that could benefit from early or more intensive anti-neoplastic therapy.Artikkelliste
Paper I. Dahlback H.S.S., Brandal, P., Meling T.R., Gorunova L., Scheie D., Heim S. Genomic Aberrations in 80 Cases of Primary Glioblastoma Multiforme: Pathogenetic Heterogeneity and Putative Cytogenetic Pathways. Genes, Chromosomes & Cancer 2009;48:908-924. The paper is removed from the thesis in DUO due to publisher restrictions. The published version is available at: https://doi.org/10.1002/gcc.20690 |
Paper II. Dahlback H.S.S., Gorunova L., Brandal, P., Scheie D., Helseth E., Meling T.R., Heim S. Genomic Aberrations in Diffuse Low-grade Gliomas. Genes, Chromosomes & Cancer 2011;50:409-420. The paper is removed from the thesis in DUO due to publisher restrictions. The published version is available at: https://doi.org/10.1002/gcc.20866 |
Paper III. Dahlback H.S.S., Gorunova L., Micci F., Scheie D., Brandal, P., Meling T.R., Heim S. Molecular Cytogenetic Analysis of a Gliosarcoma with Osseous Metaplasia”. Cytogenetic and Genome Research 2011;134:88-95. The paper is removed from the thesis in DUO due to publisher restrictions. The published version is available at: https://doi.org/10.1159/000326804 |
Paper IV. Dahlback H.S.S., Brandal, P., Krossnes B.K., Fric R., Meling T.R., Meza-Zepeda L.A., Danielsen H.E., Heim S. Multiple Monosomies Are Characteristic of Giant Cell Ependymoma. NOTICE: this is the author’s version of a work that was accepted for publication in Human Pathology. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. A definitive version was subsequently published in Human Pathology 2011;42;2042–2046. The published version of this paper is available at: https://doi.org/10.1016/j.humpath.2011.02.012 |
Paper V. Dahlback H.S.S., Brandal, P., ., Gorunova L., Widing E., Meling T.R., Krossnes B.K., Heim S. Genomic Aberrations in Paediatric Gliomas and Embryonal Tumours. Submitted version. Genes, Chromosomes & Cancer 2011;50;788–799. The published version of this paper is available at: https://doi.org/10.1002/gcc.20898 |