Panagopoulos Ioannis, Gorunova Ludmila, Bjerkehagen Bodil, Heim Sverre
Section for Cancer Cytogenetics, Institute for Cancer Genetics and Informatics, The Norwegian Radium Hospital, Oslo University Hospital, Oslo, Norway; Centre for Cancer Biomedicine, Faculty of Medicine, University of Oslo, Oslo, Norway.
Department of Pathology, The Norwegian Radium Hospital, Oslo University Hospital, Oslo, Norway.
PLoS One. 2015 Apr 14;10(4):e0124288. doi: 10.1371/journal.pone.0124288. eCollection 2015.
Retroperitoneal leiomyoma is a rare benign smooth muscle tumor almost exclusively found in women and with histopathological features similar to uterine leiomyomas. The pathogenesis of retroperitoneal leiomyoma is unclear and next to nothing is known about the cytogenetics and molecular genetics of the tumor. We present here a retroperitoneal leiomyoma with a t(9;22)(q33;q12) as the sole karyotypic aberration. The translocation resulted in an EWSR1-PBX3 fusion gene in which exon 9 of EWSR1 (nucleotide 1320 accession number NM_013986 version 3) was in-frame fused to exon 5 of PBX3 (nucleotide 824 accession number NM_006195 version 5). The EWSR1-PBX3 fusion transcript codes for a 529 amino acids long chimeric EWSR1-PBX3 protein which contains the N-terminal transactivation part of EWSR1 and the homeodomain of PBX3. The present study, together with our previous finding of a retroperitoneal leiomyoma with t(10;17)(q22;q21) as the sole karyotypic aberration and a KAT6B-KANSL1 fusion gene, indicates that retroperitoneal leiomyomas may be characterized by fusion genes coding for chimeric proteins. However, cytogenetic and molecular heterogeneity exists in these tumors and it is too early to tell how many and which different pathways lead to retroperitoneal leiomyomagenesis.
腹膜后平滑肌瘤是一种罕见的良性平滑肌肿瘤，几乎仅见于女性，其组织病理学特征与子宫平滑肌瘤相似。腹膜后平滑肌瘤的发病机制尚不清楚，关于该肿瘤的细胞遗传学和分子遗传学几乎一无所知。我们在此报告一例腹膜后平滑肌瘤，其唯一的核型异常为t(9;22)(q33;q12)。该易位导致了一个EWSR1-PBX3融合基因，其中EWSR1的第9外显子（核苷酸1320，登录号NM_013986，版本3）与PBX3的第5外显子（核苷酸824，登录号NM_006195，版本5）框内融合。EWSR1-PBX3融合转录本编码一个由529个氨基酸组成的嵌合EWSR1-PBX3蛋白，该蛋白包含EWSR1的N端反式激活部分和PBX3的同源结构域。本研究以及我们之前发现的一例以t(10;17)(q22;q21)为唯一核型异常且具有KAT6B-KANSL1融合基因的腹膜后平滑肌瘤表明，腹膜后平滑肌瘤可能以编码嵌合蛋白的融合基因为特征。然而，这些肿瘤存在细胞遗传学和分子异质性，现在判断有多少种以及哪些不同的途径导致腹膜后平滑肌瘤的发生还为时过早。
