4751

NEK2

HsPK21|NEK2A|NLK1;NIMA (never in mitosis gene a)-related kinase 2;NEK2;NIMA (never in mitosis gene a)-related kinase 2

nimA-like protein kinase 1|nimA-related protein kinase 2|serine/threonine-protein kinase Nek2

1q32.2-q41

protein-coding

We identified patterns of differentially-expressed genes in cell lines derived from several pediatric solid tumors. Affymetrix Human cancer G110 Arrays, carrying 1,700 cancer-associated genes, were applied to a panel of 11 cell linesoriginating from Ewing tumors (ETs), neuroblastomas, and malignant melanoma of soft parts. Hierarchical clustering clearly differentiated these 3 entities and revealed groups of 75, 102, and 36 gene probe-sets exhibiting tumor-type specific up-regulation in these cell lines, respectively. Whereas ET lines demonstrated increased expression of microtubule-associated protein tau (MAPT), protein phosphatase 1 regulatory subunit 1A (PPP1R1A), NIMA (never in mitosis gene a)-related kinase 2 (NEK2), and cyclin D1 (CCND1), neuroblastoma samples exhibited high expression of wingless-type mouse mammary tumor virus integrationsite family member 11 (WNT11), Drosophila frizzled homolog 2 (FZD2), and adenomatous polyposis coli (APC) which are involved in regulating free beta-catenin levels. These genes likely maintain tumor-specific characteristics and participate in key downstream regulatory mechanisms. We also correlated the expression levels of up-regulated genes in ETs with their chromosomal localization and compared these data to the comparative genomic hybridization profiles of the cell lines. We demonstrate that gains of genetic material contribute essentially to differential gene expression.

The identification of tumor antigens remains a major objective in tumor immunology, especially in pediatric malignancies where solid tumors often do notexpress a single dominant antigen. Methods such as the Serological Screening of Recombinant cDNA expression Libraries (SEREX) have been used in the discovery oftumor-expressed proteins by virtue of their ability to induce an antibody response. To focus and accelerate this approach, we first identified candidate antigens by gene expression profiling data from clinical neuroblastoma specimensand then used an animal model to generate an antibody response to an engineered cell-based vaccine. Candidate tumor antigens were expressed as recombinant proteins in a mammalian system and screened for antibody recognition using serumfrom mice vaccinated with a neuroblastoma cell-based vaccine engineered to express CD80 and CD86, with or without Treg depletion. Through this procedure, the never in mitosis A (NIMA)-related kinase NEK2 was identified as a tumor-associated antigen. Direct testing of serum from patients newly diagnosed with neuroblastoma showed specific serological responses in two of 20 patients. Although NEK2 was not universally recognized, it may serve as a tumor antigen for some patients.#CI- (c) 2010 Japanese cancer Association.