Recurrent 8q11-13 Aberrations Leading to PLAG1 Rearrangements, Including Novel Chimeras HNRNPA2B1::PLAG1 and SDCBP::PLAG1, in Lipomatous Tumors.

Background/aim: Structural abnormalities of chromosome bands 8q11-13, resulting in rearrangement of the pleomorphic adenoma gene 1 (PLAG1), are known to characterize lipoblastoma, a benign fat cell tumor, found mainly in children. Here, we describe 8q11-13 rearrangements and their molecular consequences on PLAG1 in 7 lipomatous tumors in adults.

Materials and methods: The patients were 5 males and 2 females between 23 and 62 years old. The tumors, namely five lipomas, one fibrolipoma and one spindle cell lipoma, were examined using G-banding with karyotyping, fluorescence in situ hybridization (FISH; three tumors), RNA sequencing, reverse transcription (RT) PCR, and Sanger sequencing analyses (two tumors).

Results: All 7 tumors had karyotypic aberrations which included rearrangements of chromosome bands 8q11-13 (the criterion for selection into this study). FISH analyses with a PLAG1 break apart probe showed abnormal hybridization signals in both interphase nuclei and on metaphase spreads indicating PLAG1 rearrangement. RNA sequencing detected fusion between exon 1 of heterogeneous nuclear ribonucleoprotein A2/B1 (HNRNPA2B1) and exon 2 or 3 of PLAG1 in a lipoma and fusion between exon 2 of syndecan binding protein (SDCBP) and exon 2 or 3 of PLAG1 in a spindle cell lipoma. The HNRNPA2B1::PLAG1 and SDCBP::PLAG1 fusion transcripts were confirmed using RT-PCR/Sanger sequencing analyses.

Conclusion: As 8q11-13 aberrations/PLAG1-rearrangements/PLAG1-chimeras may evidently be a defining pathogenetic feature of lipogenic neoplasms of several histological types and not just lipoblastomas, we suggest that the term "8q11-13/PLAG1-rearranged lipomatous tumors" be generally adopted for this tumor subset.