Panagopoulos Ioannis, Gorunova Ludmila, Davidson Ben, Heim Sverre
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.
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.
Cancer Lett. 2015 Feb 28;357(2):502-9. doi: 10.1016/j.canlet.2014.12.002. Epub 2014 Dec 4.
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.
多囊性间皮瘤是一种病因和发病机制不明的罕见疾病。关于这些肿瘤的细胞遗传学和分子遗传学特征，此前一无所知。在此，我们展示了首例经细胞遗传学分析的多囊性间皮瘤，其核型为46,XX,t(7;17)(p13;q23),t(8;11)(q23;p13)。RNA测序显示，t(7;17)(p13;q23)产生了一个嵌合的TNS3-MAP3K3基因，该基因编码一种嵌合蛋白激酶，以及 reciprocal MAP3K3-TNS3，其中编码SH2_Tensin_like区域和张力蛋白磷酸酪氨酸结合域的TNS3区域受MAP3K3启动子控制。另一种易位，t(8;11)(q23;p13)，产生了一个嵌合的ZFPM2-ELF5基因，该基因编码一种嵌合转录因子，其中ELF5的前40个氨基酸被ZFPM2的前100个氨基酸取代。RT-PCR与桑格测序一起验证了上述融合转录本的存在。从病变部位培养的细胞中发现获得性克隆染色体异常，以及存在TNS3-MAP3K3嵌合蛋白激酶和ZFPM2-ELF5嵌合转录因子，证实了多囊性间皮瘤的肿瘤性质。
