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Southwest Biomedical Research Institute, Scottsdale, Arizona 85281 [S. P., P. D. C., S. J-S., C. S., A. A. S., R. M. G.]; Faculté de Médecine, Nice, France [C. T-C.]; Center of Human Genetics, University of Leuven, Leuven, Belgium [P. D. C.]; University of Arizona Cancer Center and Department of Surgery, University of Arizona, Tucson, Arizona 85724 [S. P. L. L.]; and The Johns Hopkins University, Baltimore, Maryland 21205 [B. V., K. W. K.]
The q13 to q15 region of human chromosome 12 is frequently and consistently rearranged in malignant and benign adipose tissue tumors as well as benign tumors of smooth muscle and salivary glands. A reciprocal translocation, (12;16) (q13;p11), is characteristic of the myxoid subtype of liposarcoma, whereas translocations within 12q1314 are frequently observed in benign lipomas. We are using pulsed-field gel electrophoresis to study the 12q13-q14 region in order to detect and clone the respective translocation breakpoints in these tumors. The locus GLI, which encodes a zinc-finger protein, has been mapped to the same region as the myxoid liposarcoma breakpoint. Pulsed-field analysis of myxoid liposarcoma and lipoma DNA has allowed us to construct a 600-kilobase physical map surrounding the GLI locus, which shows that breakpoints in both types of tumor are outside this region. However, myxoid liposarcoma DNA samples contained altered restriction fragments detectable with GLI probes that were highly specific and reproducible from case to case. These altered fragments are due to highly specific and reproducible methylation differences that are unique to myxoid liposarcoma DNA. These methylation changes may prove to be useful clinically as a diagnostic tool to differentiate subtypes of liposarcoma.
1 This work was supported in part by NIH Grant CA-41183.
2 ARC Fellow (Association pour la Recherche contre le Cancer, Villejuif, France). Present address: Eleanor Roosevelt Institute for Cancer Research, 1899 Gaylord Street, Denver, CO 80206.
3 Recipient of the American Cancer Society Clinical Oncology Career Award.
4 To whom requests for reprints should be addressed, at Eleanor Roosevelt Institute for Cancer Research, 1899 Gaylord Street, Denver, CO 80206.
Received 7/ 9/90. Accepted 9/18/90.
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