C11orf95‐MKL2 is the resulting fusion oncogene of t(11;16)(q13;p13) in chondroid lipoma

Abstract

Chondroid lipoma, a rare benign adipose tissue tumor, may histologically resemble myxoid liposarcoma or extraskeletal myxoid chondrosarcoma, but is genetically distinct. In the current study, an identical reciprocal translocation, t(11;16)(q13;p13) was identified in three chondroid lipomas, a finding consistent with previous isolated reports. A fluorescence in situ hybridization (FISH)-based positional cloning strategy using a series of bacterial artificial chromosome (BAC) probe combinations designed to narrow the 16p13 breakpoint revealed MKL2 as the candidate gene. Subsequent 5′ RACE studies demonstrated C11orf95 as the MKL2 fusion gene partner. MKL/myocardin-like 2 (MKL2) encodes myocardin-related transcription factor B (MRTF-B) in a megakaryoblastic leukemia gene family, and C11orf95 (chromosome 11 open reading frame 95) is a hypothetical protein. Sequencing analysis of RT-PCR generated transcripts from all three chondroid lipomas defined the fusion as occurring between exons 5 and 9 of C11orf95 and MKL2, respectively. Dual-color breakpoint spanning probe sets custom-designed for recognition of the translocation event in interphase cells confirmed the anticipated rearrangements of the C11orf95 and MKL2 loci in all cases. The FISH and RT-PCR assays developed in this study can serve as diagnostic adjuncts for identification of this novel C11orf95-MKL2 fusion oncogene in chondroid lipoma.

Updates on the cytogenetics and molecular cytogenetics of benign and intermediate soft tissue tumors

“…An identical reciprocal translocation, t(11;16)(q13;p13), has been detected by cytogenetic analysis in six cases of chondroid lipoma (17)(18)(19)(20). Recurrent involvement of 11q13 has also been described in hibernoma, but not in association with 16p13 (15).…”

“…In their study, Huang et al (20) reported that the t(11;16) (q13;p13) translocation results in a fusion of C11orf95 and MKL2. These gene rearrangements have not been identified in other soft tissue tumors thus far, and appear to be characteristic for chondroid lipoma.…”

“…These gene rearrangements have not been identified in other soft tissue tumors thus far, and appear to be characteristic for chondroid lipoma. FISH assay for C11orf95 or MKL2 rearrangements is therefore useful for the differential diagnosis of chondroid lipoma and its histological mimics, particularly when evaluating small samples (20).…”

A Painless Right Supraclavicular Mass

“…Studies have suggested a link with the reciprocal translocation t(11;16)(q13;p12-13). [4][5][6] Clinically, patients present with a painless, gradually enlarging mass, most commonly located in the proximal extremities or limb girdles. 1,2 Lesions can be located in the subcutis, superficial fascia, or intermuscular and intramuscular spaces.…”

The role of HIV integration in viral persistence: no more whistling past the proviral graveyard

“…Although less studied than BACH2, it has been identified as a serum response factor (SRF) coactivator and is therefore involved in cell growth (115)(116)(117). MKL2 fusion oncogenes have also been identified, especially in chondroid lipomas, where C11orf95-MKL2 fusions are often present (118,119).…”