Recurrent fusion transcripts in squamous cell carcinomas of the vulva
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Marta Brunetti1,2, Antonio Agostini1,2, Ben Davidson3,4, Claes G Tropé5, Sverre Heim1,2,4, Ioannis Panagopoulos1,2, Francesca Micci1,2
1Section for Cancer Cytogenetics, Institute for Cancer Genetics and Informatics, The Norwegian Radium Hospital, Oslo University Hospital, Oslo, Norway
2Centre for Cancer Biomedicine, University of Oslo, Oslo, Norway
3Department of Pathology, The Norwegian Radium Hospital, Oslo University Hospital, Oslo, Norway
4Faculty of Medicine, University of Oslo, Oslo, Norway
5Department of Gynecology, The Norwegian Radium Hospital, Oslo University Hospital, Oslo, Norway
Francesca Micci, email: [email protected]
Keywords: fusion gene, promoter swapping, squamous cell carcinoma, transcriptome sequencing, PCR
Received: June 29, 2016 Accepted: January 23, 2017 Published: February 07, 2017
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.
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