MYC Messenger RNA Expression Predicts Survival Outcome in Childhood Primitive Neuroectodermal Tumor/Medulloblastoma

MYC Messenger RNA Expression Predicts Survival Outcome in Childhood Primitive Neuroectodermal Tumor/Medulloblastoma1

Divisions of Oncology [M. A. G., M. D. H., A. J. J., X. L., A. E., G. M. B., P. C. P.] and Biostatistics [H. Z.] and Departments of Neurosurgery [L. N. S.] and Pathology [L. B. R.], The Children’s Hospital of Philadelphia, Pennsylvania 19104

Abstract

Purpose and Experimental Design: Cerebellar primitive neuroectodermal tumors/medulloblastomas (PNET/MB) are the most common malignant brain tumors in childhood. To identify PNET/MB biological prognostic factors that define a patient group with a sufficiently good prognosis to permit a reduction in treatment intensity, we determined the expression levels of MYC mRNA in fresh frozen tumor samples from 26 PNET/MB patients using semiquantitative reverse transcription-PCR.

Results:MYC mRNA expression levels in primary PNET/MB showed a wide range with a 22-fold difference between the highest and lowest values and did not correlate with MYC gene amplification. MYC mRNA expression was an independent significant prognostic factor for progression-free survival outcome and was more predictive than standard clinical factors. The combination of low MYC mRNA expression and high TrkC mRNA expression identified a good outcome group of PNET/MB patients (n = 7) with 100% progression-free survival after a median follow-up time of 55 months (range, 15–91 months). Three of these seven good outcome patients survived without radiotherapy.

Conclusions: Low MYC mRNA expression is a powerful independent predictor of favorable clinical outcome in PNET/MB. Assessment of MYC mRNA levels is feasible and may be incorporated in prospective PNET/MB clinical trials to aid in treatment planning for patients with PNET/MB on confirmation of our results in larger studies.

Footnotes

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↵1 Supported by NIH Grant PO1-NS34514, the Jeffrey Miller Neuro-Oncology Research Fund, and a Career Development Award from the American Society of Clinical Oncology.
↵2 To whom requests for reprints should be addressed. Present address: University Children’s Hospital, Steinwiesstrasse 75, CH-8032 Zurich, Switzerland. Phone: 41-1-266-7111; Fax: 41-1-266-7171; E-mail: Michael.Grotzer{at}kispi.unizh.ch
↵3 The abbreviations used are: CNS, central nervous system; PNET, primitive neuroectodermal tumor; MB, medulloblastoma; RT, reverse transcription; FBS, fetal bovine serum; NB, neuroblastoma.
↵4 http://rsb.info.nih.gov/nih-image/.
- Accepted May 16, 1901.
- Received December 6, 1900.
- Revision received May 14, 1901.