Abstract
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.
Highlights
Retroperitoneal leiomyoma is a rare benign smooth muscle tumor almost exclusively found in women [1,2,3]
We searched for a fusion candidate gene up to 10 Mbp proximal to ABL1 using the genome browser of UCSC Genome Bioinformatics and found the PBX3 gene, 5 Mbp upstream of ABL1, which we deemed was the strongest candidate for further investigation as a 3 ́-partner in a EWSR1-fusion
This was because PBX3 has extensive homology to PBX1 [7] which has been found as a 3 ́-partner in an EWSR1-PBX1 fusion in myoepithelial tumors [8, 9]
Summary
Retroperitoneal leiomyoma is a rare benign smooth muscle tumor almost exclusively found in women [1,2,3]. Anatomically distinct from their uterine counterparts, they have several pathological and histological features in common with uterine leiomyomas, including hyaline fibrosis, alternating myxoid change or trabecular patterns, and positivity for estrogen and progesterone receptors [1,2,3]. The cytogenetic and molecular genetic features of retroperitoneal leiomyomas remain largely unexplored as in the 2013 edition of “WHO classification of tumours of soft tissue and bone” there is no information about the genetics of these tumors [4]. We reported the first cytogenetically analyzed retroperitoneal leiomyoma which had a PLOS ONE | DOI:10.1371/journal.pone.0124288. Fusion of the Genes EWSR1 and PBX3 in Retroperitoneal Leiomyoma t(10;17)(q22;q21) as the sole karyotypic aberration [5]. Using RNA-sequencing we could demonstrate that the molecular consequence of the translocation was fusion of the KAT6B gene on 10q22 with the KANSL1 gene (official full name: KAT8 regulatory NSL complex subunit 1) from 17q21 [5]
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