Association between high levels of expression of the TRK gene and favorable outcome in human neuroblastoma
| Autor: | Miwako Arima-Nakagawara, Alan B. Cantor, Garrett M. Brodeur, Akira Nakagawara, C G Azar, N J Scavarda |
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| Rok vydání: | 1993 |
| Předmět: |
Pathology
medicine.medical_specialty Cell Survival Molecular Sequence Data Genes myc Gene Expression Receptors Nerve Growth Factor Biology Proto-Oncogene Mas Neuroblastoma Gene expression Proto-Oncogenes medicine Tumor Cells Cultured Humans Ganglioneuroma Nerve Growth Factors RNA Messenger Child Survival rate Neoplasm Staging Messenger RNA Base Sequence Age Factors Infant General Medicine medicine.disease Prognosis Primary tumor Survival Rate Nerve growth factor nervous system Trk receptor Cancer research |
| Zdroj: | The New England journal of medicine. 328(12) |
| ISSN: | 0028-4793 |
| Popis: | The nerve growth factor receptor is expressed in some neuroblastomas, in which its primary component is encoded by the TRK protooncogene. To determine the relation of the expression of TRK messenger RNA in neuroblastomas to other clinical and laboratory variables, we studied frozen tumor samples from 77 patients. In addition, we tested two primary neuroblastomas that expressed TRK for responsiveness to nerve growth factor.TRK expression strongly correlated with favorable tumor stage (I, II, and IVS vs. III and IV), younger age (1 year vs.or = 1 year), normal N-myc copy number, and low level of N-myc expression. N-myc amplification (indicated by a high copy number) correlated with advanced tumor stage, older age, an adrenal site of the primary tumor, low level of expression of TRK, and high level of expression of N-myc. Analysis of five-year cumulative-survival rates demonstrated an association of a very favorable outcome with a high level of TRK expression (86 percent vs. 14 percent) and with normal N-myc copy number (84 percent vs. 0 percent). Univariate analysis showed that these two variables were the most powerful predictors of outcome (chi-square = 51.30, P0.001; and chi-square = 93.61, P0.001, respectively). TRK expression still had significant prognostic value when the analysis was restricted to tumors without N-myc amplification. In primary cultures of neuroblastoma cells expressing TRK, exposure to nerve growth factor induced early gene expression and neurite outgrowth, but deprivation of nerve growth factor led to neuronal cell death.A high level of expression of the TRK proto-oncogene in a neuroblastoma is strongly predictive of a favorable outcome. A tumor with a functional nerve growth factor receptor may be dependent on the neurotrophin nerve growth factor for survival and may regress in its absence, allowing a new approach to the treatment of certain patients with neuroblastoma. |
| Databáze: | OpenAIRE |
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