title: Recurrent fusion transcripts in squamous cell carcinomas of the vulva.
abstract: Juxtaposition of two different genes or gene parts due to chromosomal rearrangement is a well-known neoplasia-associated pathogenetic mechanism. The detection and characterization of such tumorigenic fusions is of great importance both research-wise, diagnostically because they may be specific for distinct tumor entities, and because they may serve as therapeutic targets for antioncogenic drugs that interact directly with the molecular changes responsible for neoplastic transformation.At present, more than 10,000 fusion transcripts have been reported in different types of neoplasia, with one tenth of them being identified in squamous cell carcinomas (SCC) of different locations. No recurrent fusion gene has to date been identified in SCC of the vulva.We performed high-throughput paired-end RNA-sequencing of 12 vulvar SCC and found two recurrent fusions with the STIP1-CREB3L1 and ZDHHC5-GPR137 being present in two tumors each. The transcripts were detected only in the tumor samples, not in normal vulvar tissue from healthy donors used as control. The CREB3L1 and ZDHHC5 genes encode proteins involved in transcription suggesting that the chimeras may alter downstream events in their respective pathways. Expression analysis of the CREB3L1 gene showed the presence of two distinct groups of tumors, one having fusion and downregulation of the gene and the other showing upregulation of CREB3L1.
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, University of Oslo, Oslo, Norway.
authors.forename: Marta
authors.initials: M
authors.lastname: Brunetti
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, University of Oslo, Oslo, Norway.
authors.forename: Antonio
authors.initials: A
authors.lastname: Agostini
authors.affiliation: Department of Pathology, The Norwegian Radium Hospital, Oslo University Hospital, Oslo, Norway.|Faculty of Medicine, University of Oslo, Oslo, Norway.
authors.forename: Ben
authors.initials: B
authors.lastname: Davidson
authors.affiliation: Department of Gynecology, The Norwegian Radium Hospital, Oslo University Hospital, Oslo, Norway.
authors.forename: Claes G
authors.initials: CG
authors.lastname: Tropé
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, University of Oslo, Oslo, Norway.|Faculty of Medicine, University of Oslo, Oslo, Norway.
authors.forename: Sverre
authors.initials: S
authors.lastname: Heim
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, University of Oslo, Oslo, Norway.
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, University of Oslo, Oslo, Norway.
authors.forename: Francesca
authors.initials: F
authors.lastname: Micci
mesh_terms: D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000473:pathology; D016022:Case-Control Studies; D017362:Cyclic AMP Response Element-Binding Protein / Q000235:genetics; D005260:Female; D006360:Heat-Shock Proteins / Q000235:genetics; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D009419:Nerve Tissue Proteins / Q000235:genetics; D015514:Oncogene Proteins, Fusion / Q000235:genetics*; D043562:Receptors, G-Protein-Coupled / Q000235:genetics; D014846:Vulvar Neoplasms / Q000235:genetics* / Q000473:pathology
chemical_list: C485618:CREB3L1 protein, human; D017362:Cyclic AMP Response Element-Binding Protein; D006360:Heat-Shock Proteins; D009419:Nerve Tissue Proteins; D015514:Oncogene Proteins, Fusion; D043562:Receptors, G-Protein-Coupled; C079373:STIP1 protein, human
keywords: PCR; fusion gene; promoter swapping; squamous cell carcinoma; transcriptome sequencing