{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,12]],"date-time":"2026-02-12T16:14:08Z","timestamp":1770912848913,"version":"3.50.1"},"reference-count":47,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2012,4,18]],"date-time":"2012-04-18T00:00:00Z","timestamp":1334707200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes Chromosomes &amp;amp; Cancer"],"published-print":{"date-parts":[[2012,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Neuroblastoma (NB) is the most common and lethal extracranial solid tumor of childhood. Despite aggressive therapy, more than half of the children with advanced NB will die of uncontrolled metastatic disease. After chemotherapy, tumor\u2010initiating cells (TICs) could persist, cause relapses and metastasis. The aim of this study is to demonstrate the tumor\u2010initiating properties of CD133<jats:sup>high<\/jats:sup> NB cells and to identify new specific genetic abnormalities. Isolation of the CD133<jats:sup>high<\/jats:sup> cell population from NB cell lines was followed by neurosphere formation, soft agar assays, and orthotopic injections in NOD\/SCID\/IL2R\u03b3c\u2010null mice. A differential genotyping analysis was performed with Affymetrix SNP 6.0 arrays on CD133<jats:sup>low<\/jats:sup> and CD133<jats:sup>high<\/jats:sup> populations and the frequency of the abnormalities of 36 NB tumors was determined. Our results show that CD133<jats:sup>high<\/jats:sup> NB cells possess tumor\u2010initiating properties, as CD133<jats:sup>high<\/jats:sup> cells formed significantly more neurospheres and produced significantly more colonies in soft agar than CD133<jats:italic><jats:sup>low<\/jats:sup><\/jats:italic>. Injection of 500 CD133<jats:sup>high<\/jats:sup> cells was sufficient to generate primary tumors and frequent metastases in mice. Differential genotyping analysis demonstrated two common regions with gains (16p13.3 and 19p13.3) including the gene <jats:italic>EFNA2<\/jats:italic> in the CD133<jats:sup>high<\/jats:sup> population, and two with loss of heterozygosity (16q12.1 and 21q21.3) in the CD133<jats:italic><jats:sup>low<\/jats:sup><\/jats:italic> population. The gain of <jats:italic>EFNA2<\/jats:italic> correlated with increased expression of the corresponding protein. These abnormalities were found in NB samples and some were significantly correlated with CD133 expression. Our results show that CD133<jats:sup>high<\/jats:sup> NB cells have TICs properties and present different genotyping characteristics compared to CD133<jats:italic><jats:sup>low<\/jats:sup><\/jats:italic> cells. Our findings reveal insights into new therapeutic targets in NB TICs. \u00a9 2012 Wiley Periodicals, Inc.<\/jats:p>","DOI":"10.1002\/gcc.21964","type":"journal-article","created":{"date-parts":[[2012,4,18]],"date-time":"2012-04-18T13:06:17Z","timestamp":1334754377000},"page":"792-804","source":"Crossref","is-referenced-by-count":17,"title":["Genotype analysis of tumor\u2010initiating cells expressing CD133 in 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