Prognostic significance of NPM-ALK fusion transcript overexpression in ALK-positive anaplastic large-cell lymphoma
Prognostic significance of NPM-ALK fusion transcript overexpression in ALK-positive anaplastic large-cell lymphoma
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DOI：
10.1038/modpathol.3800781
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发表时间：
2007-06-01
期刊：
影响因子：
7.5
通讯作者：
Inagaki, Hiroshi
中科院分区：
文献类型：
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作者：
Li, Chunmei;Takino, Hisashi;Inagaki, Hiroshi
在间变性淋巴瘤激酶（ALK）蛋白阳性的间变性大细胞淋巴瘤中，ALK基因最常与NPM基因融合，较少与TPM3、TFG、ATIC和其他罕见基因融合。虽然这种淋巴瘤通常与良好的临床结果相关，但25%的患者在5年内死于该疾病。在这项研究中，我们开发了三种检测方法，所有这些方法都可以用于档案福尔马林固定石蜡包埋的组织：(1)灵敏的逆转录聚合酶链反应（RT-PCR）检测各种X-ALK融合基因，(2)cDNA末端50快速扩增（RACE）检测未知融合伙伴，(3)实时RT-PCR检测定量nmp - alk融合转录物的数量。在26例ALK（+）间变性大细胞淋巴瘤中，RT-PCR检测显示ALK与NPM融合21例，与TPM3融合3例，与TFG融合1例。50 RACE检测剩余病例的ATIC-ALK融合。实时定量RT-PCR分析显示，在20例可量化的病例中，有4例NPM-ALK转录物过表达。与NPM-ALK低表达的患者相比，NPM-ALK过表达的患者总体生存期明显不利。本文开发的RT-PCR和50 RACE检测方法可用于鉴定与ALK基因融合的已知和未知基因伴侣。NPM-ALK融合转录物的过表达可能与ALK（+）间变性大细胞淋巴瘤患者预后不良有关。
In anaplastic large-cell lymphomas positive for anaplastic lymphoma kinase (ALK) protein, the ALK gene is most commonly fused to the NPM gene, and less commonly to TPM3, TFG, ATIC, and other rare genes. Although this lymphoma is generally associated with a favorable clinical outcome, 25% of the patients die of the disease within 5 years. In this study, we developed three assays, all of which can be used with archival formalin-fixed, paraffin-embedded tissues: (1) a sensitive reverse transcription-polymerase chain reaction (RT-PCR) assay for various X-ALK fusion genes, (2) a 50 rapid amplification of cDNA ends (RACE) assay to identify unknown fusion partners, and (3) a real-time RT-PCR assay to quantify the amount of the NPM-ALK fusion transcript. In 26 cases of ALK(+) anaplastic large-cell lymphoma, the RT-PCR assay showed that the ALK was fused to NPM in 21 cases, to TPM3 in three, and to TFG in one. The 50 RACE assay detected ATIC-ALK fusion in the remaining case. The real-time quantitative RT-PCR assay showed that the NPM-ALK transcript was over expressed in four of 20 quantifiable cases. Patients with NPM-ALK overexpression showed a significantly unfavorable overall survival compared with those with a low expression of this transcript. The RT-PCR and 50 RACE assays developed here may be useful for identification of known and unknown gene partners fused to the ALK gene. Overexpression of the NPM-ALK fusion transcript may be associated with a poor prognosis of the patients with ALK(+) anaplastic large-cell lymphomas.