Association of Multiple Copies of the N-<i>myc</i>Oncogene with Rapid Progression of Neuroblastomas

TLDR

The study examined 89 untreated primary neuroblastoma patients to assess how N‑myc copy number relates to progression‑free survival. Amplification of N‑myc (3–300 copies) was found in most Stage III and IV tumors and correlated with markedly worse progression‑free survival—18‑month rates fell from 70 % with one copy to 5 % with >10 copies—and was linked to faster progression and higher metastasis rates, indicating that N‑myc amplification drives neuroblastoma aggressiveness. N Engl J Med 1985; 313:1111–6.

Abstract

Eighty-nine patients with untreated primary neuroblastomas were studied to determine the relation between the number of copies of the N-myc oncogene and survival without disease progression. Genomic amplification (3 to 300 copies) of N-myc was detected in 2 of 16 tumors in Stage II, 13 of 20 in Stage III, and 19 of 40 in Stage IV; in contrast, 8 Stage I and 5 Stage IV-S tumors all had 1 copy of the gene (P<0.01). Analysis of progression-free survival in all patients revealed that amplification of N-myc was associated with the worst prognosis (P<0.0001); the estimated progression-free survival at 18 months was 70 per cent, 30 per cent, and 5 per cent for patients whose tumors had 1, 3 to 10, or more than 10 N-myc copies, respectively. Of 16 Stage II tumors, 2 with amplification metastasized, whereas only 1 of 14 without amplification did so (P = 0.03). Stage IV tumors with amplification progressed most rapidly: nine months after diagnosis the estimated progression-free survival was 61 per cent, 47 per cent, and 0 per cent in patients whose tumors had 1, 3 to 10, or more than 10 copies, respectively (P<0.0001). These results suggest that genomic amplification of N-myc may have a key role in determining the aggressiveness of neuroblastomas. (N Engl J Med 1985; 313: 1111–6.)