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Molecular Analysis of Deletions of the Short Arm of Chromosome 9 in Human Gliomas¹

Section of Hematology/Oncology, Department of Medicine, University of Chicago, Chicago, Illinois 60637 [O. I. O., K. M., H. P., J. D. R., M. O. D.]; Section of Laboratory Genetics, Department of Laboratory Medicine and Pathology, Mayo Clinic and Mayo Foundation, Rochester, Minnesota 55905 [R. B. J., D. T. R.]; Department of Paediatrics/Genetics, Virginia Medical School, Norfolk, Virginia 23507 [J. M. C.]; and Department of Medicine, University of California, San Diego, California 92093 [T. N.]

Previous studies have suggested that structural abnormalities involving the short arm of chromosome 9 are frequently associated with gliomas. The -, ß-, and -interferon (IFNA, IFNB1, and IFNW, respectively) and the methylthioadenosine phosphorylase (MTAP) genes have been mapped to the short arm of chromosome 9, band p22. Homozygous deletions of these genes have been reported in many leukemia- and glioma-derived cell lines. In this report, we present a detailed analysis of partial and complete homozygous or hemizygous deletions of DNA sequences on 9p in human cell lines and primary tumor samples of glioma patients. Ten of 15 (67%) glioma-derived cell lines had hemizygous or homozygous deletion of IFN genes or rearrangement of sequences around these genes, while 13 of 35 (37%) primary glioma tumor samples had hemizygous (8 tumors) or homozygous (5 tumors) deletion of the IFN genes. The shortest region of overlap of these deletions maps in the interval between the centromeric end of the IFN gene cluster and the MTAP gene. In the cell lines and primary tumors examined, these gross genomic alterations were seen only in association with high grade or recurrent gliomas. Our observations confirm that loss of DNA sequences on 9p, particularly the IFN genes, occurs at a significant frequency in gliomas, and may represent an important step in the progression of these tumors. These results are consistent with a model of tumorigenesis in which the development or progression of cancer involves the loss or inactivation of a gene or several genes that normally act to suppress tumorigenesis. One such gene may be located on 9p; this gene may be closely linked to the IFN genes. Nevertheless, loss of the IFN genes, when it occurs, may play an additional role in the progression of these tumors.

¹ The work was supported in part by the Department of Health and Human Services, Grants CA49133, CA42557, and CA50905; Association for Brain Tumor Research/Ellen Ruth Lebow Fellowship; Rochester Eagle's Cancer Research Foundation; and the University of Chicago Cancer Research Center.

² To whom requests for reprints should be addressed, at The Department of Medicine, Section of Hematology/Oncology, University of Chicago, 5841 South Maryland Avenue, Box 420, Chicago, IL 60637.

Received 10/23/91. Accepted 2/19/92.

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