Novel TNS3-MAP3K3 and ZFPM2-ELF5 fusion genes identified by RNA sequencing in multicystic mesothelioma with t(7;17)(p12;q23) and t(8;11)(q23;p13)

Ioannis Panagopoulos; Ludmila Gorunova; Ben Davidson; Sverre Heim

doi:10.1016/j.canlet.2014.12.002

Novel TNS3-MAP3K3 and ZFPM2-ELF5 fusion genes identified by RNA sequencing in multicystic mesothelioma with t(7;17)(p12;q23) and t(8;11)(q23;p13)

Cancer Lett. 2015 Feb 28;357(2):502-9. doi: 10.1016/j.canlet.2014.12.002. Epub 2014 Dec 4.

Authors

Ioannis Panagopoulos¹, Ludmila Gorunova², Ben Davidson³, Sverre Heim⁴

Affiliations

¹ Section for Cancer Cytogenetics, Institute for Cancer Genetics and Informatics, The Norwegian Radium Hospital, Oslo University Hospital, Montebello, PO Box 49534, Nydalen, NO-0424, Oslo 0310, Norway; Centre for Cancer Biomedicine, Faculty of Medicine, University of Oslo, Oslo, Norway. Electronic address: ioannis.panagopoulos@rr-research.no.
² Section for Cancer Cytogenetics, Institute for Cancer Genetics and Informatics, The Norwegian Radium Hospital, Oslo University Hospital, Montebello, PO Box 49534, Nydalen, NO-0424, Oslo 0310, Norway; Centre for Cancer Biomedicine, Faculty of Medicine, University of Oslo, Oslo, Norway.
³ Department of Pathology, The Norwegian Radium Hospital, Oslo University Hospital, Oslo, Norway; Faculty of Medicine, University of Oslo, Oslo, Norway.
⁴ Section for Cancer Cytogenetics, Institute for Cancer Genetics and Informatics, The Norwegian Radium Hospital, Oslo University Hospital, Montebello, PO Box 49534, Nydalen, NO-0424, Oslo 0310, Norway; Centre for Cancer Biomedicine, Faculty of Medicine, University of Oslo, Oslo, Norway; Faculty of Medicine, University of Oslo, Oslo, Norway.

PMID: 25484136
DOI: 10.1016/j.canlet.2014.12.002

Abstract

Multicystic mesothelioma is a rare disease of unknown etiology and pathogenesis. Nothing has been known about the cytogenetic and molecular genetic features of these tumors. Here we present the first cytogenetically analyzed multicystic mesothelioma with the karyotype 46,XX,t(7;17)(p13;q23),t(8;11)(q23;p13). RNA-sequencing showed that the t(7;17)(p13;q23) generated a chimeric TNS3-MAP3K3 gene, which codes for a chimeric protein kinase, as well as the reciprocal MAP3K3-TNS3 in which the region of TNS3 coding for the SH2_Tensin_like region and the tensin phosphotyrosine-binding domain is under the control of the MAP3K3 promoter. The other translocation, t(8;11)(q23;p13), generated a chimeric ZFPM2-ELF5 gene which codes for a chimeric transcription factor in which the first 40 amino acids of ELF5 are replaced by the first 100 amino acids of ZFPM2. RT-PCR together with Sanger sequencing verified the presence of the above-mentioned fusion transcripts. The finding of acquired clonal chromosome abnormalities in cells cultured from the lesion and the presence of the TNS3-MAP3K3 chimeric protein kinase and the ZFPM2-ELF5 chimeric transcription factor confirm the neoplastic nature of multicystic mesothelioma.

Keywords: Chimeric protein kinase; Chimeric transcription factor; Cytogenetics; Fusion genes; Multicystic mesothelioma; RNA sequencing.

Publication types

Case Reports
Research Support, Non-U.S. Gov't

MeSH terms

Adult
Base Sequence
Chromosome Banding
Chromosomes, Human, Pair 11 / genetics
Chromosomes, Human, Pair 17 / genetics
Chromosomes, Human, Pair 7 / genetics
Chromosomes, Human, Pair 8 / genetics
DNA-Binding Proteins / genetics*
Diagnosis, Differential
Female
Gene Expression Regulation, Neoplastic
Humans
In Situ Hybridization, Fluorescence
Karyotype
MAP Kinase Kinase Kinase 3 / genetics*
Mesothelioma, Cystic / diagnosis
Mesothelioma, Cystic / genetics*
Mesothelioma, Cystic / surgery
Microfilament Proteins / genetics*
Molecular Sequence Data
Oncogene Proteins, Fusion / genetics
Proto-Oncogene Proteins c-ets / genetics*
Reverse Transcriptase Polymerase Chain Reaction
Sequence Analysis, RNA / methods
Tensins
Transcription Factors / genetics*
Translocation, Genetic*

Substances

DNA-Binding Proteins
ELF5 protein, human
Microfilament Proteins
Oncogene Proteins, Fusion
Proto-Oncogene Proteins c-ets
TNS3 protein, human
TNS3-MAP3K3 fusion protein, human
Tensins
Transcription Factors
ZFPM2 protein, human
ZFPM2-ELF5 fusion protein, human
MAP Kinase Kinase Kinase 3
MAP3K3 protein, human