Clinical implications of oncogene activation in human neuroblastomas

Amplification of the oncogene N‐myc has been identified in almost all human neuroblastoma cell lines tested. Eighty‐nine primary neuroblastomas from untreated patients were studied to determine the frequency and clinical significance of N‐myc amplification. Tumor DNA was analyzed by hybridization with the radiolabeled probe pNB‐1 for N‐myc. Amplification (3–300 copies) of the N‐myc gene was found in 34 of the 89 tumors (38%). Amplification was not found in 8 Stage I or 5 Stage IV‐S tumors, but it was found in 2 of 16 with Stage II, 13 of 20 with Stage III, and 19 of 40 with Stage IV tumors (P < 0.01). Correlation of N‐myc amplification with progression‐free survival (PFS) indicated that N‐myc amplification was associated with a worse prognosis (P < 0.0001). The PFS at 18 months was 70%, 30%, and 5% for patients whose tumors had 1, 3–10, and more than 10 copies, respectively. Even within individual stages, the presence of N‐myc amplification correlated with rapid progression. For instance, of 16 patients with Stage II disease, the 2 with N‐myc amplification developed progressive disease rapidly, whereas only 1 of 14 without amplification progressed (P = 0.03). Similarly, those with Stage HI and IV disease whose tumors have multiple copies of N‐myc had a substantially worse prognosis. The correlation between N‐myc amplification and age at diagnosis was also analyzed. Although N‐myc amplification was detected in only 4 of 28 infants less than 1 year of age, compared to 30 of 61 older patients (P < 0.005), this difference disappeared when corrected for disease stage. The results suggest that N‐myc amplification is a powerful prognostic indicator, and that this gene may play an important role in the progression of certain neuroblastomas. Cancer 58:541‐545, 1986.

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