Novel CSF1-S100A10 fusion gene and CSF1 transcript identified by RNA sequencing in tenosynovial giant cell tumors

• DOI: 10.3892/ijo.2014.2326
• Publication Date: 2014-03-05T12:45:04Z
• Authors: IOANNIS PANAGOPOULOS; PETTER BRANDAL; LUDMILA GORUNOVA; BODIL BJERKEHAGEN; SVERRE HEIM
• Keywords: Male; Base Sequence; Oncogene Proteins, Fusion; Sequence Analysis, RNA; Macrophage Colony-Stimulating Factor; Giant Cell Tumors; Molecular Sequence Data; S100 Proteins; Intracellular Signaling Peptides and Proteins; High-Throughput Nucleotide Sequencing; Exons; Article; 03 medical and health sciences; 0302 clinical medicine; Chromosomes, Human, Pair 1; Cell Line, Tumor; MCF-7 Cells; Humans; Female; RNA, Messenger; 3' Untranslated Regions; Annexin A2; HeLa Cells

RNA-sequencing was performed on three tenosynovial giant cell tumors (TSGCT) in an attempt to elicit more information on the mechanisms of CSF1 expression in this tumor type. A novel CSF1-S100A10 fusion gene was found in a TSGCT that carried the translocation t(1;1)(q21;p11) as the sole karyotypic abnormality. In this fusion gene, the part of CSF1 coding for the CSF1 protein (exons 1-8 in sequences with accession nos. NM_000757 and NM_172212) is fused to the 3'-part of S100A10. Since the stop codon TAG of CSF1 is present in it, the CSF1-S100A10 fusion gene's predominant consequence seems to be the replacement of the 3'-untranslated region (UTR) of CSF1 (exon 9; nt 2092-4234 in sequence with accession no. NM_000757 or nt 2092-2772 in NM_172212) by the 3'-end of S100A10 (exon 3; nt 641-1055 in sequence with accession no. NM_002966). In the other two TSGCT, a novel CSF1 transcript was detected, the same in both tumors. Similar to the occurrence in the CSF1-S100A10 fusion gene, the novel CSF1 transcript 3'-UTR is replaced by a new exon located ~48 kb downstream of CSF1 and 11 kb upstream of AHCYL1. Although only 3 TSGCT were available for study, the finding in all of them of a novel CSF1-S100A10 fusion gene or CSF1 transcript indicates the existence of a common pathogenetic theme in this tumor type: the replacement of the 3'-UTR of CSF1 with other sequences.