Myxoid Liposarcoma

A number sign (#) is used with this entry because myxoid liposarcoma can be caused by chromosomal translocations, most commonly t(12;16)(q13;p11) (Panagopoulos et al., 1996).

Myxoid liposarcoma is a soft tissue tumor that tends to occur in the limbs (especially the thigh) of patients ranging in age from 35 to 55 years. It is defined by the presence of a hypocellular spindle cell proliferation set in a myxoid background, often with mucin pooling. Lipoblasts tend to be small and often monovacuolated and to cluster around vessels or at the periphery of the lesion (review by Dei Tos, 2000).

Limon et al. (1986) and Turc-Carel et al. (1986) described a specific chromosome change, t(12;16)(q13;p11), in the tumors of all 4 cases of myxoid liposarcoma studied. One patient had a history of multiple lipomatosis. A relationship to the INT1 oncogene on chromosome 12 or to a fragile site on that chromosome was suggested. Turc-Carel et al. (1987) found, however, by Southern blot analysis of DNA from 2 myxoid liposarcomas carrying the translocation t(12;16)(q13;p11), that the translocation did not disrupt the INT1 gene (164820). In 9 different solitary subcutaneous lipomas, all with clonal abnormalities affecting 12q13-q15, Arheden et al. (1989) found no rearrangement or amplification of the INT1 gene. Karakousis et al. (1987) found the specific translocation between chromosomes 12 and 16 in 5 cases of myxoid liposarcoma. Walter et al. (1988) and Bridge et al. (1988) reported a 12;16 translocation in myxoid liposarcoma. See also Smith et al. (1987) and Mertens et al. (1987).

Mandahl et al. (1987) studied 10 consecutive lipomas; supernumerary ring chromosomes were found in 3; balanced rearrangements in 6; and a normal karyotype in 1. Chromosome 12 was involved in 5 of the balanced rearrangements and probably in all the ring chromosomes, with breakpoints localized to 12q13 or 12q14. They suggested that the development of myxoid liposarcoma requires the recombination of 2 specific chromosome bands, 12q13 and 16p11, whereas for some types of benign lipogenic tumors structural changes in 12q13-q14 may be sufficient for neoplastic growth. In a follow-up study of 25 additional solitary lipomas, Mandahl et al. (1988) found supernumerary ring chromosomes in 2 cases; balanced rearrangements involving 12q13-q14 in 8; hypodiploid or diploid chromosomes involving aberrations other than rings or rearrangements of 12q13-q14 in 7; and normal karyotypes in 8.

Heim et al. (1988) concluded, on the basis of cytogenetic analysis of tumor cells from 50 lipomas, that 4 main cytogenetic subtypes can be recognized: (1) tumors with normal karyotype (18 cases); (2) tumors with rearrangements of 12q13-q14 (18 cases); (3) tumors with ring chromosomes (6 cases); and (4) tumors with other clonal changes (8 cases). All 6 tumors with ring marker chromosomes were histopathologically classified as atypical lipomas. All 7 multiple lipomas were karyotypically normal.

Eneroth et al. (1990) narrowed the localization of the chromosome breaks in t(12;16) of myxoid liposarcomas to 12q13.3 and 16p11.2.

Mrozek et al. (1993) demonstrated that the chromosome 12 breakpoint in benign lipoma (151900) is at 12q15, whereas the breakpoint in myxoid liposarcoma is at 12q13.3.

CHOP (DDIT3)/FUS (TLS) Fusion Gene

Aman et al. (1992) used the Southern blot technique to demonstrate that CHOP (126337), a gene of the CCAAT/enhancer binding protein (C/EBP) family which maps to 12q13 and is assumed to be involved in adipocyte differentiation, is rearranged in myxoid liposarcomas. Rabbitts et al. (1993) demonstrated that the translocation t(12;16)(q13;p11) in malignant liposarcoma can result in a fusion of the CHOP dominant-negative transcription factor gene with a novel gene called FUS (137070).

CHOP/EWS Fusion Gene

In an analysis of peripheral blood samples from 19 patients with myxoid liposarcoma due to t(12;16) and in 1 patient with myxoid liposarcoma due to t(12;22;20), resulting in the fusion of the CHOP and EWS (133450) genes, Panagopoulos et al. (1996) found FUS/CHOP hybrid fragments in 3 patients with t(12;16) and an EWS/CHOP hybrid in the patient with the latter translocation.