Recurrent fusion transcripts in squamous cell carcinomas of the vulva.
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.
['Brunetti|Marta|M|', 'Agostini|Antonio|A|', 'Davidson|Ben|B|', 'Tropé|Claes G|CG|', 'Heim|Sverre|S|', 'Panagopoulos|Ioannis|I|', 'Micci|Francesca|F|']
D002294:Carcinoma, Squamous Cell D016022:Case-Control Studies D017362:Cyclic AMP Response Element-Binding Protein D005260:Female D006360:Heat-Shock Proteins D059014:High-Throughput Nucleotide Sequencing D006801:Humans D009419:Nerve Tissue Proteins D015514:Oncogene Proteins, Fusion D043562:Receptors, G-Protein-Coupled D014846:Vulvar Neoplasms
squamous cell carcinoma fusion gene PCR promoter swapping transcriptome sequencing