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'- non-coding 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.

Keywords: Aneurysmal bone cyst; LUM; LUM-USP6 fusion gene; USP6; chromosome translocation.

Figure 1. Microscopic examination of the aneurysmal bone cyst. A) Hematoxylin and eosin (H&E) stained section showing compact growth of fibrous tissue with spindled cells and focal areas with scattered osteoclast-like giant cells, magnification 20×. B) H&E stained section showing cystic space and osteoid production with focal calcification, magnification 20×.

Figure 2. G-banding and FISH analyses. A) Karyogram of the aneurysmal bone cyst cells showing the der(12)t(12;17)(q21;p13) and der(17)t(12;17)(q21;p13). Breakpoint positions are indicated by arrows. B) FISH with the USP6 break-apart probe on metaphase spread showing that the distal part of the probe (green signal) hybridized to the der(12)t(12;17)(q21;p13) whereas the proximal part of the probe (red signal) hybridized to der(17)t(12;17)(q21;p13). Both distal and proximal parts of the USP6 probe hybridized to the normal chromosome 17.

Figure 3. Results of Sanger sequencing. Partial sequence chromatograms of the cDNA amplified fragment showing the junction position of the LUM and USP6 genes (arrow). The exon numbers were based on the sequences with accession numbers NM_002345.4 for LUM and NM_001304284.2 for USP6.