Behrends Uta, Schneider Inken, Rössler Sabine, Frauenknecht Heinrich, Golbeck Anja, Lechner Brigitte, Eigenstetter Gerhard, Zobywalski Colette, Müller-Weihrich Stephan, Graubner Ulrike, Schmid Irene, Sackerer Dieter, Späth Manfred, Goetz Claudia, Prantl Franz, Asmuss Hans-Peter, Bise Karl, Mautner Josef
Kinderklinik, Hämatologie-Onkologie, Technische Universität, München, Germany.
Int J Cancer. 2003 Aug 20;106(2):244-51. doi: 10.1002/ijc.11208.
Medulloblastoma is an embryonal childhood malignancy with poor prognosis. By screening 4 medulloblastoma cDNA expression libraries (SEREX) with autologous sera, 15 different antigens were identified. These antigens were encoded by 3 novel genes, genes of unknown function (KIAA0445, KIAA1853, KIAA0665, FLJ13942, HSPC213), a proto-oncogene (rab18), candidate tumor suppressor genes (BAP1, 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 HCA58 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 1 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.
髓母细胞瘤是一种预后较差的儿童胚胎性恶性肿瘤。通过用自体血清筛选4个髓母细胞瘤cDNA表达文库（SEREX），鉴定出了15种不同的抗原。这些抗原由3个新基因、功能未知基因（KIAA0445、KIAA1853、KIAA0665、FLJ13942、HSPC213）、一个原癌基因（rab18）、候选肿瘤抑制基因（BAP1、PRDM13）以及编码运动蛋白（驱动蛋白-2）、组蛋白（H2A1.2）、富含锚蛋白残基的鼻咽癌易感蛋白（NZ16）和转录因子TZP的基因编码，其中TZP与肿瘤相关抗原HCA58和GLEA2同源。在对血清抗体滴度和肿瘤负荷的连续分析中，一名侵袭性大细胞髓母细胞瘤患者血清中针对PRDM13的抗体增加了10倍以上，先于复发性肿瘤生长的临床诊断。当检测40名癌症患儿患者和40名健康对照者的血清对SEREX定义抗原的体液反应时，有5种抗原仅被癌症患者的血清识别。这些抗原包括一种从以前被描述为3'非翻译区的mRNA序列翻译而来的新型rab18基因产物。在其余10种抗原中的2种抗原的体液反应在癌症患者中更为常见。分别在8/40和12/40的癌症患者中检测到针对这些抗原的抗体，但仅在1名健康对照者中检测到。这2种抗原分别具有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反应针对的是多种抗原，这些抗原可能作为诊断标志物或免疫治疗靶点。
