Souzaki Ryota, Tajiri Tatsuro, Teshiba Risa, Higashi Mayumi, Kinoshita Yoshiaki, Tanaka Sakura, Taguchi Tomoaki
Department of Pediatric Surgery, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, Japan.
Pediatr Surg Int. 2011 Mar;27(3):231-6. doi: 10.1007/s00383-010-2781-4.
MYCN amplification (MYCN-A) is a strong prognostic factor in neuroblastoma (NB). MYCN gain which is a low level of MYCN-A as determined by FISH. It is unclear whether the MYCN gain is the pre-status of MYCN-A. This study assessed the status of MYCN gene and chromosome 2p of MYCN-A, MYCN gain and no MYCN amplification using a single nucleotide polymorphism (SNP) array, and the clinical implication of MYCN gain in NB.
The status of the MYCN gene was determined by FISH in 47 primary NB samples and the status of chromosome 2p in all cases was analyzed using an SNP array.
8 of the 47 cases analyzed using FISH showed MYCN-A, 7 cases showed MYCN gain and 32 cases showed no MYCN amplification. An SNP array analysis showed that only 2 of 8 cases with MYCN-A by FISH had both amplification of MYCN region and distal 2p gain and other 6 cases had amplification of the MYCN region without distal 2p gain. All 7 cases with MYCN gain by FISH had distal 2p gain without amplification of the MYCN region, and all 32 cases with no MYCN amplification by FISH demonstrated neither the amplification of the MYCN region nor the 2p gain. 5-year overall survival rate of patients with MYCN gain (n = 7, 71.4%) was not significant different from that of patients with no MYCN amplification (n = 32, 90.6%) by FISH (p = 0.11).
These results suggested that the MYCN gain detected by FISH represents the 2p gain, and the MYCN gain is not considered to represent the pre-status of MYCN amplification.
MYCN基因扩增（MYCN-A）是神经母细胞瘤（NB）的一个重要预后因素。MYCN获得性改变是指通过荧光原位杂交（FISH）检测到的低水平MYCN-A。目前尚不清楚MYCN获得性改变是否是MYCN-A的前期状态。本研究使用单核苷酸多态性（SNP）芯片评估了MYCN-A、MYCN获得性改变和无MYCN基因扩增情况下MYCN基因及2号染色体短臂（2p）的状态，以及MYCN获得性改变在NB中的临床意义。
采用FISH检测47例原发性NB样本中MYCN基因的状态，并使用SNP芯片分析所有病例中2号染色体短臂的状态。
在47例经FISH分析的病例中，8例显示MYCN-A，7例显示MYCN获得性改变，32例显示无MYCN基因扩增。SNP芯片分析显示，在8例经FISH检测为MYCN-A的病例中，仅2例同时存在MYCN区域扩增和2p远端增益，其他6例仅有MYCN区域扩增而无2p远端增益。所有7例经FISH检测为MYCN获得性改变的病例均有2p远端增益但无MYCN区域扩增，所有32例经FISH检测无MYCN基因扩增的病例既无MYCN区域扩增也无2p增益。经FISH检测，MYCN获得性改变患者（n = 7，71.4%）的5年总生存率与无MYCN基因扩增患者（n = 32，90.6%）相比，差异无统计学意义（p = 0.11）。
这些结果表明，FISH检测到的MYCN获得性改变代表2p增益，且MYCN获得性改变不被认为是MYCN基因扩增的前期状态。
