Behrends Uta, Jandl Thomas, Golbeck Anja, Lechner Brigitte, Müller-Weihrich Stephan, Schmid Irene, Till Holger, Berthold Frank, Voltz Raymond, Mautner Josef M
Hämatologie-Onkologie, Kinderklinik der Technische Universität München, Kölner Platz 1, 80804 Munich, Germany.
Int J Cancer. 2002 Aug 20;100(6):669-77. doi: 10.1002/ijc.10550.
Autologous serological screening of a cDNA expression library (SEREX) derived from childhood neuroblastoma led to the identification of 10 different antigens, including 6 novel gene products. The novel antigen 018INX was derived from a small open reading frame in a region of alpha-internexin mRNA that was previously described as 3' untranslated region. 018INX thus represents a novel type of tumor antigen. Five novel gene products were derived from NNP-1 (NNP3) and Hu genes (HuC-L, HuD3, HuDY, HuD1pro(c)). As indicated by sequence analysis, these antigens were generated by alternative splicing and/or alternative promoter usage or allelic polymorphism. mRNA expression analyses revealed different tissue restrictions of novel compared to known HuD and NNP-1 transcripts in normal and malignant tissues. The expressions patterns of distinct transcripts indicated potential clinical meanings as diagnostic and/or prognostic tissue markers. When kinetics of serum antibody titres against SEREX-defined antigens were compared to tumor load over time in our patient with neuroblastoma, we found 100-fold increases of anti-Hu and anti-018INX antibody titres preceding the clinical diagnosis of recurrent tumor growth after 2 years. When sera of pediatric patients with cancer (30) and healthy controls (30) were tested for humoral responses to SEREX-defined neuroblastoma antigens, we detected antibodies against all known antigens and NNP3 with low frequencies and titres in control sera, while anti-018INX and anti-Hu antibodies were found in cancer patients only. Our findings indicate that SEREX-defined tumor antigens might provide novel tools for understanding and treatment of this aggressive childhood malignancy.
对源自儿童神经母细胞瘤的cDNA表达文库进行自体血清学筛选（SEREX），鉴定出10种不同的抗原，其中包括6种新的基因产物。新抗原018INX源自α-中间丝蛋白mRNA区域的一个小开放阅读框，该区域先前被描述为3'非翻译区。因此，018INX代表一种新型肿瘤抗原。5种新的基因产物源自NNP-1（NNP3）和Hu基因（HuC-L、HuD3、HuDY、HuD1pro(c)）。序列分析表明，这些抗原是通过可变剪接和/或可变启动子使用或等位基因多态性产生的。mRNA表达分析显示，与正常组织和恶性组织中已知的HuD和NNP-1转录本相比，新转录本具有不同的组织限制性。不同转录本的表达模式表明其作为诊断和/或预后组织标志物具有潜在的临床意义。在我们的神经母细胞瘤患者中，将针对SEREX定义抗原的血清抗体滴度动力学与肿瘤负荷随时间的变化进行比较时，我们发现在临床诊断复发性肿瘤生长前2年，抗Hu和抗018INX抗体滴度增加了100倍。当检测30名癌症儿童患者和30名健康对照者的血清对SEREX定义的神经母细胞瘤抗原的体液反应时，我们在对照血清中检测到针对所有已知抗原和NNP3的抗体，其频率和滴度较低，而仅在癌症患者中发现了抗018INX和抗Hu抗体。我们的研究结果表明，SEREX定义的肿瘤抗原可能为理解和治疗这种侵袭性儿童恶性肿瘤提供新工具。
