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| SOMATIC MUTATIONS IN THE NEUROFIBROMATOSIS-1 GENE IN HUMAN TUMORS |
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| Author(s): LI Y, BOLLAG G, CLARK R, STEVENS J, CONROY L, FULTS D, WARD K, FRIEDMAN E, SAMOWITZ W, ROBERTSON M, BRADLEY P, MCCORMICK F, WHITE R, CAWTHON R |
| Source: CELL Volume: 69 Issue: 2 Pages: 275-281 Published: APR 17 1992 |
| Times Cited: 270 References: 37 |
| Abstract: The neurofibromatosis 1 (NF1) gene product, neurofibromin, contains a GTPase-activating protein (GAP)-related domain, or NF1 GRD, that is able to down-regulate p21ras by stimulating its intrinsic GTPase. Since p21ras-GTP is a major regulator of growth and differentiation, mutant neurofibromins resulting from somatic mutations in the NF1 gene might interfere with ras signaling pathways and contribute to the development of tumors. We describe an amino acid substitution in the NF1 GRD, altering Lys-1423, that has occurred in three tumor types: colon adenocarcinoma, myelodysplastic syndrome, and anaplastic astrocytoma, and in one family with neurofibromatosis 1. The GAP activity of the mutant NF1 GRD is 200- to 400-fold lower than that of wild type, whereas binding affinity is unaffected. Thus, germline mutations in NF1 that cause neurofibromatosis 1 can also occur in somatic cells and contribute to the development of sporadic tumors, including tumors not associated with neurofibromatosis 1. |
| Document Type: Article |
| Language: English |
| Reprint Address: LI, Y (reprint author), UNIV UTAH, SCH MED, DEPT HUMAN GENET, SALT LAKE CITY, UT 84112 USA |
Addresses:
1. UNIV UTAH, SCH MED, HOWARD HUGHES MED INST, SALT LAKE CITY, UT 84112 USA
2. UNIV UTAH, SCH MED, DEPT NEUROSURG, SALT LAKE CITY, UT 84112 USA
3. UNIV UTAH, SCH MED, HUMAN MOLEC BIOL & GENET PROGRAM, SALT LAKE CITY, UT 84112 USA
4. UNIV UTAH, SCH MED, ECCLES INST HUMAN GENET, SALT LAKE CITY, UT 84112 USA
5. UNIV UTAH, SCH MED, DEPT OBSTET & GYNECOL, SALT LAKE CITY, UT 84112 USA
6. UNIV UTAH, SCH MED, DNA DIAGNOST LAB, SALT LAKE CITY, UT 84112 USA
7. UNIV UTAH, SCH MED, DEPT PATHOL, SALT LAKE CITY, UT 84112 USA
8. CHIRON CORP, DEPT MOLEC BIOL, EMERYVILLE, CA 94608 USA
9. KAROLINSKA INST, DEPT CLIN GENET, S-10401 STOCKHOLM 60, SWEDEN |
| Publisher: CELL PRESS, 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 |
| Subject Category: Biochemistry & Molecular Biology; Cell Biology |
| IDS Number: HQ183 |
| ISSN: 0092-8674 |
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| | | | | | | | | Record from Web of Science® | | | | | | | | | |