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Allelotype of Human Malignant Astrocytoma¹

Division of Neurosurgery, Department of Surgery [D. F., C. A. P.], Department of Pediatrics [G. A. T.], Howard Hughes Medical Institute [G. A. T., R. W.], and Department of Human Genetics [R. W.], University of Utah, Salt Lake City, Utah 84132

Astrocytoma, the most common brain tumor in humans, is usually malignant and virtually incurable. Two types of malignant astrocytomas can be distinguished histopathologically: anaplastic astrocytoma and glioblastoma multiforme. Studies using DNA markers that detect restriction fragment length polymorphisms have shown that loci on chromosomes 10 and 17p are lost frequently in tumor DNA from malignant astrocytoma patients, suggesting that tumor suppressor genes important in astrocytoma tumorigenesis may be present on 2 different chromosomes. To identify additional regions of chromosome loss, we carried out an allelotype analysis of 41 malignant astrocytoma patients using restriction fragment length polymorphism markers for each arm of every human autosome. Loss of heterozygosity was found for every autosome except chromosome 21, indicating an even greater complexity of genomic alterations than reported previously. Many tumors showed loss of heterozygosity for multiple chromosomes and the number of chromosomes involved correlated with tumor histopathology. A high-resolution restriction fragment length polymorphism study of chromosome 10 loci in these patients showed that loss of broad regions of chromosome 10 was a common event, particularly in glioblastoma multiforme. An allelotype analysis has been carried out on only one other tumor, human colorectal carcinoma. Different profiles of allele loss were observed in malignant astrocytoma and colorectal carcinoma, suggesting that the genetic events leading to these 2 human cancers may proceed along different pathways.

¹ This work was supported by NIH Clinical Investigator Award CA01049 (D. F.), American Cancer Society Research Grant CD-404 (D. F.), and American Cancer Society Clinical Oncology Career Development Award 89-183 (G. A. T.).

² To whom requests for reprints should be addressed, at Division of Neurosurgery, University of Utah School of Medicine, 50 North Medical Drive, Salt Lake City, UT 84132.

³ Investigator of the Howard Hughes Medical Institute.

Received 4/25/90. Accepted 6/19/90.

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