Fusion of the Lumican (LUM) Gene With the Ubiquitin Specific Peptidase 6 (USP6) Gene in an Aneurysmal Bone Cyst Carrying a t(12;17)(q21;p13) Chromosome Translocation

Abstract

Background/Aim: Aneurysmal bone cyst is a benign bone lesion with a strong tendency to recur. The rearrangement of chromosome band 17p13/USP6 gene is now considered a characteristic genetic feature of aneurysmal bone cyst, with t(16;17)(q22;p13)/CDH11-USP6 as the most frequent chromosomal aberration/fusion gene. We report a novel variant translocation leading to a new fusion gene in an aneurysmal bone cyst. Materials and Methods: Genetic analyses were performed on an aneurysmal bone cyst found in the tibia of a child. Results: G-banding chromosome analysis yielded the karyotype 46,XX,t(12;17)(q21;p13)[5]/46,XX[2]. FISH analysis with a USP6 break-apart probe showed rearrangement of USP6. RNA sequencing detected LUM-USP6 and USP6-LUM fusion transcripts which were subsequently verified by RT-PCR/Sanger sequencing. The two genes exchanged 5'-noncoding exons. Thus, promoter swapping between USP6 and LUM had taken place. Conclusion: We report a novel t(12;17)(q21;p13) chromosome translocation which gave rise to a LUM-USP6 fusion in an aneurysmal bone cyst. Aneurysmal bone cyst is a rapidly expanding, benign bone lesion with a strong tendency to recur (1-3). It is found in all age groups but most commonly during the first two decades of 555 This article is freely accessible online.

Recurrent Fusion of the Genes for High-mobility Group AT-hook 2 (HMGA2) and Nuclear Receptor Co-repressor 2 (NCOR2) in Osteoclastic Giant Cell-rich Tumors of Bone

“…Aneurysmal bone cysts are pathogenetically characterized by rearrangements of chromosome band 17p13 targeting the ubiquitin-specific protease 6 gene (USP6 or Tre2) resulting in fusions in which USP6 is the 3' moiety, but where the promoter of USP6 is replaced by a stronger promoter from the partner fusion gene so that USP6 becomes transcriptionally up-regulated (3)(4)(5)(6)(7)(8). The chromosome translocation t(16;17)(q22;p13) is the most frequent cytogenetic aberration reported (21%) in aneurysmal bone cysts with an abnormal karyotype (9).…”

“…The chromosome translocation t(16;17)(q22;p13) is the most frequent cytogenetic aberration reported (21%) in aneurysmal bone cysts with an abnormal karyotype (9). It generates a fusion gene in which the strong promoter of the cadherin 11 gene (CDH11) from 16q21 fuses with the USP6 coding sequence from 17p13 (6,7) leading to a CDH11-USP6 chimera in which the USP6 gene is transcriptionally up-regulated (3,4).…”

Tumors and infections of the growing spine

“…However, the cause of ABCs remains unknown; recently, primary ABCs have been associated with a translocation resulting into the activation of the ubiquitin-specific peptidase 6 (USP6) gene on chromosome 17. 40,50,51 ABCs may have an unpredictable behavior, with a high recurrence rate after intralesional treatment. 48,52 The treatment of ABC is controversial, with surgical and nonsurgical options described in the literature.…”

“…However, the cause of ABCs remains unknown; recently, primary ABCs have been associated with a translocation resulting into the activation of the ubiquitin-specific peptidase 6 (USP6) gene on chromosome 17. 40 , 50 , 51 …”

Neoplasia-associated Chromosome Translocations Resulting in Gene Truncation

“…A chimera may also demonstrate promoter swapping when the translocation breakpoints occur in the 5′, non-coding end of the genes. This leads to deregulation of the involved genes, again possibly resulting in oncogenesis (7)(8)(9)(10)(11)(12)(13)(14)(15). In B-and T-lineage lymphatic leukemias and lymphomas, one partner of the fusion gene typically codes for an immunoglobulin or T-cell receptor; the other partner gene becomes quantitatively deregulated when it comes under the control of elements whose normal function it is to maintain steady transcription of the immunoglobulin and/or T-cell receptor genes (1).…”