ASSOCIATION OF MULTIPLE COPIES OF THE N-MYC ONCOGENE WITH RAPID PROGRESSION OF NEUROBLASTOMAS
ASSOCIATION OF MULTIPLE COPIES OF THE N-MYC ONCOGENE WITH RAPID PROGRESSION OF NEUROBLASTOMAS
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DOI：
10.1056/nejm198510313131802
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发表时间：
1985-01-01
影响因子：
158.5
通讯作者：
HAMMOND, D
中科院分区：
文献类型：
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作者：
SEEGER, RC;BRODEUR, GM;HAMMOND, D
研究了89例未经治疗的原发性神经母细胞瘤患者，以确定N-myc癌基因拷贝数与无疾病进展生存之间的关系。16例II期患者中有2例，20例III期患者中有13例，40例IV期患者中有19例检测到N-myc基因组扩增（3 - 300拷贝）；8例I期和5例IV-S期肿瘤均有1个拷贝（P < 0.01）。所有患者的无进展生存分析显示，N-myc扩增与最差预后相关（P < 0.0001）；对于N-myc拷贝数分别为1、3至10或超过10的患者，18个月时的无进展生存率分别为70%、30%和5%。在16例II期肿瘤中，2例扩增发生转移，而14例未扩增的肿瘤中只有1例发生转移（P = 0.03）。伴有扩增的IV期肿瘤进展最快；诊断后9个月，肿瘤拷贝数为1、3 ~ 10或大于10的患者的无进展生存率分别为61%、47%和0% （P < 0.0001）。这些结果表明，基因组N-myc扩增可能在决定神经母细胞瘤的侵袭性中起关键作用。
Eight-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%, 30%, and 5% 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%, 47%, and 0% 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.