Alaminos Miguel, Gerald William L, Cheung Nai-Kong V
Department of Pathology, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, New York 10021, USA.
Pediatr Blood Cancer. 2005 Dec;45(7):909-15. doi: 10.1002/pbc.20505.
The molecular mechanisms driven by overexpression of the MYCN gene in neuroblastoma are not well known. Whether MYCN overexpression in the absence of genomic amplification, or ID2 overexpression has prognostic value remains controversial.
Ninety-nine neuroblastic tumors from Memorial Sloan-Kettering Cancer Center and 12 neuroblastoma cell lines were analyzed by Affymetrix U95v2 Microarray System. The expression levels of the genes MYCN and ID2 were determined by RT-PCR and immunohistochemistry and the clinical value of the overexpression of both genes was determined.
MYCN genomic amplification with overexpression was prognostic for survival (P = 0.0005). Stage 4 patients with MYCN amplification but without overexpression, had no increased likelihood of death, whereas cases with MYCN overexpression but no genomic amplification showed a low survival (P = 0.0096). ID2 did not correlate with MYCN expression (R = -0.23 for tumors and -0.27 for cell lines) or with survival (P = 0.8746).
MYCN amplification was not related to clinical outcome in the absence of overexpression in neuroblastoma tumors. ID2 expression appears to be independent of MYCN expression and lacks prognostic value.
MYCN基因在神经母细胞瘤中过表达所驱动的分子机制尚不清楚。在无基因组扩增情况下MYCN过表达或ID2过表达是否具有预后价值仍存在争议。
采用Affymetrix U95v2微阵列系统对纪念斯隆凯特琳癌症中心的99例神经母细胞瘤肿瘤和12种神经母细胞瘤细胞系进行分析。通过逆转录聚合酶链反应(RT-PCR)和免疫组织化学测定MYCN和ID2基因的表达水平,并确定这两种基因过表达的临床价值。
MYCN基因组扩增伴过表达对生存具有预后意义(P = 0.0005)。4期MYCN扩增但无过表达的患者死亡可能性未增加,而MYCN过表达但无基因组扩增的病例生存率较低(P = 0.0096)。ID2与MYCN表达无关(肿瘤的R = -0.23,细胞系的R = -0.27),也与生存无关(P = 0.8746)。
在神经母细胞瘤肿瘤中,若无过表达,MYCN扩增与临床结局无关。ID2表达似乎独立于MYCN表达,且缺乏预后价值。