title: Sequential combination of karyotyping and RNA-sequencing in the search for cancer-specific fusion genes.
abstract: Cancer-specific fusion genes are often caused by cytogenetically visible chromosomal rearrangements such as translocations, inversions, deletions or insertions, they can be the targets of molecular therapy, they play a key role in the accurate diagnosis and classification of neoplasms, and they are of prognostic impact. The identification of novel fusion genes in various neoplasms therefore not only has obvious research importance, but is also potentially of major clinical significance. The "traditional" methodology to detect them began with cytogenetic analysis to find the chromosomal rearrangement, followed by utilization of fluorescence in situ hybridization techniques to find the probe which spans the chromosomal breakpoint, and finally molecular cloning to localize the breakpoint more precisely and identify the genes fused by the chromosomal rearrangement. Although laborious, the above-mentioned sequential approach is robust and reliable and a number of fusion genes have been cloned by such means. Next generation sequencing (NGS), mainly RNA sequencing (RNA-Seq), has opened up new possibilities to detect fusion genes even when cytogenetic aberrations are cryptic or information about them is unknown. However, NGS suffers from the shortcoming of identifying as "fusion genes" also many technical, biological and, perhaps in particular, clinical "false positives," thus making the assessment of which fusions are important and which are noise extremely difficult. The best way to overcome this risk of information overflow is, whenever reliable cytogenetic information is at hand, to compare karyotyping and sequencing data and concentrate exclusively on those suggested fusion genes that are found in chromosomal breakpoints. This article is part of a Directed Issue entitled: Rare Cancers.
authors.affiliation: Section for Cancer Cytogenetics, Institute for Cancer Genetics and Informatics, The Norwegian Radium Hospital, Oslo University Hospital, Oslo, Norway; Centre for Cancer Biomedicine, Faculty of Medicine, University of Oslo, Oslo, Norway. Electronic address: ioannis.panagopoulos@rr-research.no.
authors.forename: Ioannis
authors.initials: I
authors.lastname: Panagopoulos
authors.affiliation: Section for Cancer Cytogenetics, Institute for Cancer Genetics and Informatics, The Norwegian Radium Hospital, Oslo University Hospital, Oslo, Norway; Centre for Cancer Biomedicine, Faculty of Medicine, University of Oslo, Oslo, Norway.
authors.forename: Jim
authors.initials: J
authors.lastname: Thorsen
authors.affiliation: Section for Cancer Cytogenetics, Institute for Cancer Genetics and Informatics, The Norwegian Radium Hospital, Oslo University Hospital, Oslo, Norway; Centre for Cancer Biomedicine, Faculty of Medicine, University of Oslo, Oslo, Norway.
authors.forename: Ludmila
authors.initials: L
authors.lastname: Gorunova
authors.affiliation: Section for Cancer Cytogenetics, Institute for Cancer Genetics and Informatics, The Norwegian Radium Hospital, Oslo University Hospital, Oslo, Norway; Centre for Cancer Biomedicine, Faculty of Medicine, University of Oslo, Oslo, Norway.
authors.forename: Francesca
authors.initials: F
authors.lastname: Micci
authors.affiliation: Section for Cancer Cytogenetics, Institute for Cancer Genetics and Informatics, The Norwegian Radium Hospital, Oslo University Hospital, Oslo, Norway; Centre for Cancer Biomedicine, Faculty of Medicine, University of Oslo, Oslo, Norway.
authors.forename: Sverre
authors.initials: S
authors.lastname: Heim
mesh_terms: D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007621:Karyotyping; D015514:Oncogene Proteins, Fusion / Q000235:genetics* / Q000302:isolation & purification; D012313:RNA / Q000235:genetics; D014178:Translocation, Genetic
chemical_list: D015514:Oncogene Proteins, Fusion; D012313:RNA
keywords: Cancer-specific fusion genes; Karyotyping; RNA-sequencing