Most myxoid liposarcomas (MLS) are characterized cytogenetically by a t( 12; I6)(q I3:p I I). It is reasonable t o assume that this translocation corresponds t o the consistent rearrangement of one o r t w o genes in 12q I 3 and/or I6p I I, and that the loci thus affected are important in the normal control of fat cell differentiation and proliferation. W e have used Southern blot technique t o test whether a gene of the CCAAT/enhancer binding protein (C/EBP) family, CHOP, which maps t o 12q I3 and is assumed t o be involved in adipocyte differentiation, could be the 12q gene in question. Using a cDNA probe that spans the CHOP coding region, we detected one rearranged and one wild type allele in nine of nine MLS with t( 12; 16). Using PCR generated, site-specific probes corresponding to the non-coding exons I and 2 and intron 2 of CHOP, rearrangements in five of seven tumors mapped to the 2.4 and I .6 kbp Pstl fragments that contain the first t w o exons and introns of the gene and the upstream promoter region. In contrast t o the findings in MLS, no tumor without a t( 12; 16) exhibited aberrant CHOP restriction digest patterns. These tumors included one highly differentiated liposarcoma with abnormal katyotype but no involvement of I2q 13, seven lipomas with various cytogenetic aberrations of 12q 13-15, two uterine leiomyomas with t( 12; 14) (q 14-I5;q23-24), and one hemangiopericytoma and one chondroma. both of which also had 12q I 3 changes. These findings demonstrate that the 12q breakpoint of the t( 12; 16) in MLS differs from those in the other tumors investigated, even in cases with no cytogenetically visible differences in breakpoint position, that CHOP rearrangement is specific for MLS, and that the breakpoints cluster t o the 5' region of the gene. W e assume that the CHOP alteration is an important step in MLS tumorigenesis and speculate that this is achieved by interference with the normal function of the C/EBP family of transcription factors. Genes Chrorn Cancer 9278-285 ( / 992). @) 1992 Wiley-Liss. Inc.