Novel tumor antigens identified by autologous antibody screening of childhood medulloblastoma cDNA libraries
Novel tumor antigens identified by autologous antibody screening of childhood medulloblastoma cDNA libraries
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DOI：
10.1002/ijc.11208
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发表时间：
2003-08-20
影响因子：
6.4
通讯作者：
Mautner, J
中科院分区：
文献类型：
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作者：
Behrends, U;Schneider, I;Mautner, J
髓母细胞瘤是一种预后不良的胚胎性儿童恶性肿瘤。用自体血清筛选4个髓母细胞瘤cDNA表达文库（SEREX），鉴定IS不同抗原。这些抗原由3个新基因编码，这些基因的功能未知（KIAA 0445、KIAA 18 S3、KIAA 066 S、FLJ 13942、HSPC 213）、原癌基因（rab 18）、候选肿瘤抑制基因（BAPI，PRDM 13）和编码马达蛋白的基因（驱动蛋白-2），一种组蛋白（H2A1.2）、富含锚蛋白残基的鼻咽癌易感蛋白（NZ 16）和转录因子TZP，其与肿瘤相关抗原HCAS 8和GLEA 2同源。在血清抗体滴度和肿瘤负荷的连续分析中，在侵袭性大细胞髓母细胞瘤患者中，在复发性肿瘤生长的临床诊断之前，针对PRDM 13的血清抗体增加超过10倍。当测试患有癌症的儿科患者（n = 40）和健康对照（n = 40）的血清针对SEREX定义的抗原的体液应答时，5种抗原仅被来自癌症患者的血清识别。这些抗原包括一种新的rab 18基因产物，该产物由以前描述为3'非翻译区的mRNA序列翻译而来。对其余10种抗原中的2种的体液应答优先在癌症患者中发现。分别在8/40和12/40名癌症患者中检测到针对这些抗原的抗体，但仅在1名健康对照中检测到。这2种抗原的特征分别为肿瘤特异性缺失和肿瘤特异性突变。这些发现表明，针对髓母细胞瘤的体液免疫应答针对不同的抗原，这些抗原可用作诊断标记物或免疫治疗的靶点。(C)2003 Wiley-Liss，Inc.
Medulloblastoma is an embryonal childhood malignancy with poor prognosis. By screening 4 medulloblastoma cDNA expression libraries (SEREX) with autologous sera, IS different antigens were identified. These antigens were encoded by 3 novel genes, genes of unknown function (KIAA0445, KIAA18S3, KIAA066S, FLJ13942, HSPC213), a proto-oncogene (rab18), candidate tumor suppressor genes (BAPI, PRDM13) and genes encoding a motor protein (kinesin-2), a histone (H2A1.2), the ankyrin residue-rich nasopharyngeal cancer susceptibility protein (NZ16) and the transcription factor TZP, which is homologous to the tumor-associated antigens HCAS8 and GLEA2. In a consecutive analysis of serum antibody titers and tumor load, a more than 10-fold increase in serum antibodies against PRDM13 preceded the clinical diagnosis of recurrent tumor growth in a patient with aggressive large cell medulloblastoma. When sera of pediatric patients with cancer (n = 40) and healthy controls (n = 40) were tested for humoral responses against the SEREX-defined antigens, 5 antigens were exclusively recognized by sera from cancer patients. These antigens included a novel rab18 gene product translated from mRNA sequences formerly described as 3' untranslated region. Humoral responses against 2 of the remaining 10 antigens were found preferentially in cancer patients. Antibodies against these antigens were detected in 8/40 and 12/40 cancer patients, respectively, but in only I healthy control. The 2 antigens were characterized by a tumor-specific deletion and a tumor-specific mutation, respectively. These findings indicate that the humoral immune response against medulloblastoma is directed against diverse antigens that may be useful as diagnostic markers or targets for immunotherapy. (C) 2003 Wiley-Liss, Inc.