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| ANALYSIS OF THE FUNCTIONAL-ROLE OF CHROMOSOME-10 LOSS IN HUMAN GLIOBLASTOMAS |
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| Author(s): PERSHOUSE MA, STUBBLEFIELD E, HADI A, KILLARY AM, YUNG WKA, STECK PA |
| Source: CANCER RESEARCH Volume: 53 Issue: 20 Pages: 5043-5050 Published: OCT 15 1993 |
| Times Cited: 75 References: 45 |
| Abstract: 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. |
| Document Type: Article |
| Language: English |
Addresses:
1. UNIV TEXAS, MD ANDERSON CANC CTR, DEPT NEUROONCOL, BOX 316, 1515 HOLCOMBE BLVD, HOUSTON, TX 77030 USA
2. UNIV TEXAS, MD ANDERSON CANC CTR, DEPT GENET, HOUSTON, TX 77030 USA
3. UNIV TEXAS, MD ANDERSON CANC CTR, DEPT LAB MED, HOUSTON, TX 77030 USA
4. UNIV TEXAS, MD ANDERSON CANC CTR, CTR BRAIN TUMOR, HOUSTON, TX 77030 USA |
| Publisher: AMER ASSOC CANCER RESEARCH, PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 |
| Subject Category: Oncology |
| IDS Number: MB993 |
| ISSN: 0008-5472 |
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