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 GLI oncogene, discovered by virtue of its amplification in human tumors, encodes a sequence-specific DNA-binding protein containing five zinc fingers. We have now characterized one member of a family of GLIrelated zinc finger genes. A previously identified fragment of GLI3 genomic DNA was used to localize GLI3 to chromosome 7p13 and to isolate cDNA clones. Sequence analysis of these clones and identification of the GLI3 protein by using polyclonal antisera demonstrated that GLI3 encodes a protein of 1,596 amino acids and an apparent molecular mass of 190 kilodaltons. Amino acid sequence comparison with GLI demonstrated seven regions of similarity (53 to 88% identity), with the zinc fingers representing the most similar region. Furthermore, when produced in vitro, the GLI3 protein bound specifically to genomic DNA fragments containing GLI-binding sites. Amino acid sequence comparison with the product of another member of the GLI family, the Drosophila segment polarity gene cubitus interruptus Dominant, revealed additional similarity that was not shared with GLI. These studies suggest that the GLI-related genes encode a family of DNA-binding proteins with related target sequence specificities. In addition, sequence similarity aside from the zinc finger region suggests that other aspects of function are shared among the members of this gene family.DNA-binding transcription factors are important in both neoplasia and normal development. Analysis of various DNA-binding proteins has allowed their classification into subgroups based on the structure of the DNA-binding domains. One major class of DNA-binding proteins contains the helix-tun-helix motif first identified in the lambda repressor (44) and subsequently identified in homeobox proteins (30,41). A second class of transcription factors contains the zinc finger repeats first identified in the Xenopus transcription factor TFIIIA (15,25). Another class of DNAbinding proteins utilizes the leucine zipper and adjacent residues to mediate dimerization of protein molecules and DNA binding (26,29,50). Other types of DNA-binding motifs continue to be described (e.g., references 17 and 37).The GLI gene was isolated by virtue of its amplification in a human glioma (22) and was subsequently found to be amplified in other tumor types (40; unpublished observations). GLI has been shown to transform primary rodent cells in vitro in conjunction with adenovirus EIA, supporting the hypothesis that GLI gene amplification in primary human tumors is important in the neoplastic process (J. M. Ruppert, B. Vogelstein, and K. W. Kinzler, submitted for publication). The protein encoded by GLI was shown to be nuclear, with five zinc fingers related to those of the Xenopus transcription factor TFIIIA and to the product of the Drosophila segmentation gene Kruppel (23,24). Using a polymerase chain reaction-based approach, we isolated several GLIbinding sites from the human genome (24). Taken together, these results suggest that GLI may act to transform cells by binding to specific DNA seque...

We have investigated cytogenetically a total of 35 solitary lipomas, 10 of which have been reported previously. Of the 25 tumours presented herein for the first time, clonal chromosome aberrations were detected in 17. The remaining eight had normal karyotypes, although two of them had nonclonal aberrations in about one quarter of the cells. Based on the cytogenetic findings in all 35 lipomas, four major subgroups can be distinguished. These are characterized by: (I) hyperdiploid karyotypes including one or more supernumerary ring chromosomes (5 cases); (II) diploid karyotypes with mostly balanced rearrangements involving 12q13-14 (13 cases), including the rearrangement t(3;12) (q27-28;q13-14) in 4 cases; (III) hypodiploid or diploid karyotypes with other aberrations than ring chromosomes or rearrangements of 12q13-14 (8 cases); and (IV) normal karyotypes (9 cases).

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Seventy‐nine acute myeloid leukemias (AML) and myelodysplastic syndromes without cytogenetic evidence of 12p aberrations were investigated by fluorescence in situ hybridization with probes for ETV6 and CDKN1B (previously called TEL and KIP1, respectively) to ascertain whether abnormalities of these genes are frequently undetected by standard chromosome banding analyses and, if so, whether they are associated with specific karyotypic patterns and morphologic features. One of sixty cytogenetically aberrant myeloid malignancies, an AML with a complex karyotype including del(5q) and del(20q), showed a hemizygous interstitial deletion of the ETV6 and CDKN1B loci. No concomitant rearrangement of the other ETV6 allele was detected. Two of nineteen cytogenetically normal AML displayed a hemizygous interstitial deletion involving CDKN1B, but not ETV6. Thus, cryptic deletions of these genes seem to be rare in cytogenetically abnormal myeloid malignancies without 12p aberrations (2%), whereas they may be more frequent in karyotypically normal AML (10%). Furthermore, the present findings show that the deletions may be narrow, not including the ETV6 gene, and indirectly suggest that CDKN1B, or a closely located genomic segment, is the target of 12p deletions. Genes Chromosom. Cancer 19:77–83, 1997. © 1997 Wiley‐Liss, Inc.