Rearrangement of the transcription factor gene CHOP in myxoid liposarcomas with t(12;16)(q13;p11)

Abstract

Most myxoid liposarcomas (MLS) are characterized cytogenetically by a t(12;16)(q13;p11). It is reasonable to assume that this translocation corresponds to the consistent rearrangement of one or two genes in 12q13 and/or 16p11, and that the loci thus affected are important in the normal control of fat cell differentiation and proliferation. We have used Southern blot technique to test whether a gene of the CCAAT/enhancer binding protein (C/EBP) family, CHOP, which maps to 12q13 and is assumed to 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 1 and 2 and intron 2 of CHOP, rearrangements in five of seven tumors mapped to the 2.4 and 1.6 kbp PstI fragments that contain the first two exons and introns of the gene and the upstream promoter region. In contrast to 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 karyotype but no involvement of 12q13, seven lipomas with various cytogenetic aberrations of 12q13-15, two uterine leiomyomas with t(12;14) (q14-15;q23-24), and one hemangiopericytoma and one chondroma, both of which also had 12q13 changes.(ABSTRACT TRUNCATED AT 250 WORDS)

The myxoid liposarcoma FUS-DDIT3 fusion oncoprotein deregulates NF-κB target genes by interaction with NFKBIZ

“…The MLS cell line MLS 402-91 (Å man et al, 1992;ThelinJa¨rnum et al, 1999) and human fibrosarcoma cell lines HT1080, HT1080 DDIT3-GFP and HT1080 FUS-DDIT3-GFP (Engstro¨m et al, 2006) were kept frozen in liquid nitrogen or cultured at 37 1C and 5% CO 2 in RPMI 1640 medium with HEPES (4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid) buffer supplemented with 2 mM L-glutamine, 50 U/ml penicillin, 50 mg/ml streptomycin and 8% fetal calf serum (Invitrogen, Carlsbad, CA, USA). G418 (200 mg/ml, Invitrogen) was constantly added to cell lines HT1080 FUSA-GFP, HT1080 DDIT3-GFP and HT1080 FUS-DDIT3-GFP to ensure stable expression of GFP constructs in the cell population.…”

HMGA2 Regulates Transcription of the Imp2 Gene via an Intronic Regulatory Element in Cooperation with Nuclear Factor-κB

“…(27) have shown that HMGA2 protein suppression results in growth inhibition of HMGA2-overexpressing primary cell cultures of well-differentiated liposarcoma, indicating that HMGA2 plays an important role in the growth of these tumors. The cytogenetic hallmark of myxoid liposarcoma is the presence of t(12;16)(q13;p11) that leads to the formation of the FUS-DDIT3 fusion protein (28)(29)(30)(31). In contrast to well-differentiated liposarcoma, the HMGA2 gene is not amplified in myxoid liposarcoma.…”

Molecular and cytogenetics of soft tissue sarcomas

“…(also referred to as TLS for translocated in liposarcoma) (Aman et al 1992, Rabbits et al 1993. The CHOP gene possesses a leucine zipper dimerization domain, whereby the protein can bind to C/EBP-like proteins and block their interaction with DNA.…”