[52] MGC3032-MKL2 Is the Resulting Fusion Oncogene of t(11;16)(q13;p13) in Chondroid Lipoma

D Huang, J Sumegi, JD Reith, P Dal Cin, T Yasuda, M Nelson, JA Bridge. University of Nebraska Medical Center, Omaha, NE; Cincinnati Children's Hospital Medical Center, Cincinnati, OH; University of Florida College of Medicine, Gainesville, FL; Brigham and Women's Hospital, Boston, MA

Background: Chondroid lipoma (ChL), a rare benign adipose tissue tumor, may histologically resemble myxoid liposarcoma or myxoid chondrosarcoma. In the current study, cytogenetic analysis of 3 ChLs revealed a t(11;16)(q13;p13) in all 3 cases, a finding consistent with previous isolated reports. We hypothesized that this primary translocation generates a fusion gene of central pathogenic relevance in ChL. Our study objectives were to: 1) further localize the t(11;16) chromosomal breakpoints in ChL; 2) uncover the underlying involved genes; and, 3) establish new molecular diagnostic assays for ChL.
Design: A fluorescence in situ hybridization (FISH)-based positional cloning strategy using a series of bacterial artificial chromosome (BAC) probe combinations on ChL abnormal metaphase cells was employed for narrowing the t(11;16) breakpoints. Following identification of MKL2 as the candidate gene on 16p13, MKL2 gene specific primers were designed and 5' RACE studies conducted. Subsequently, all 3 ChLs were subjected to RT-PCR analysis using fusion transcript specific primers followed by sequencing. Lastly, interphase FISH studies were also performed on all 3 cases utilizing newly established dual fusion probe sets.
Results: Metaphase FISH analysis revealed single BAC probes covering the chromosome 11 and 16 breakpoint regions; the latter corresponding to the MKL2 gene locus. 5' RACE identified MGC3032 as the MKL2 partner gene and sequencing studies of the RT-PCR generated transcripts defined the fusion occurring between exons 5 and 9 of MGC3032 and MKL2 respectively. Identical fusion transcripts were confirmed in all 3 ChL cases. Interphase FISH studies showed the anticipated rearrangements of the MGC3032 and MKL2 loci.
Conclusions: ChL is characterized by chromosomal translocation t(11;16)(q13.1;p13) resulting in the fusion of the MGC3032 and MKL2 genes. Megakaryoblastic leukemia 2 (MKL2) encodes for myocardin-related transcription factor B (MRTF-B) in a megakaryoblastic leukemia gene family, and MGC3032 is a hypothetical protein. Additional studies must be conducted to determine the functionality of this unique MGC3032-MKL2 fusion oncogene in ChL. Novel FISH and RT-PCR assays developed in this study can serve as diagnostic adjuncts for this rare entity.
Category: Bone & Soft Tissue

Monday, March 9, 2009 8:15 AM

Platform Session: Section E, Monday Morning