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Analysis of the Functional Role of Chromosome 10 Loss in Human Glioblastomas¹

Departments of Neuro-Oncology [M. A. P., A. H., W. K. A. Y., P. A. S.], Genetics [E. S.], and Laboratory Medicine [A. M. K.], and The Brain Tumor Center [M. A. P., A. H., W. K. A. Y., P. A. S.], The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030

Molecular and cytogenetic analyses of primary brain tumors have shown that losses on chromosome 10 occur very frequently in human glioblastoma multiforme suggesting the presence of a glioma-associated tumor suppressor gene on this chromosome. To examine this hypothesis, a copy of chromosome 10 derived from a human fibroblast cell line was introduced into the human glioma cell line U251 by microcell-mediated chromosomal transfer. A human chromosome 2 was also independently introduced into U251 cells. The presence of novel chromosomes or chromosomal fragments was confirmed by molecular and karyotypic analyses. The hybrid clones containing a transferred chromosome 10 exhibited a suppression of their transformed and tumorigenic phenotype in vivo and in vitro, whereas cells containing a transferred chromosome 2 failed to alter their phenotype. The hybrid cells containing a transferred chromosome 10 displayed a significant decrease in their saturation density and an altered cellular morphology at high cell density but only a slight decrease in their exponential growth rate. A dramatic decrease was observed in the ability of cells with an introduced chromosome 10 to grow in soft agarose. The introduction of chromosome 10 completely suppressed tumor formation when the hybrid cells were injected into nude mice. These findings indicate that chromosome 10 harbors a tumor suppressor gene that is directly involved in glioma oncogenesis.

¹ Supported in part by National Cancer Institute Grants RO1 CA56041, R55 CA56041, and RO1 CA51148; a grant from The Gilland Foundation; and Cancer Center Core Grant NCI CA-16672.

² To whom requests for reprints should be addressed, at Department of Neuro-Oncology, The University of Texas M. D. Anderson Cancer Center, Box 316, 1515 Holcombe Blvd., Houston, TX 77030.

Received 5/27/93. Accepted 8/11/93.

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