IN THE SPOTLIGHT Apples to Origins : Identifying Brain Tumor Stem Cell Genes by Comparing Transcriptomes of Normal and Cancer Stem Cells

492 | CANCER DISCOVERY JUNE 2012 www.aacrjournals. org Authors’ Affi liation: Department of Pathology, The Pediatric Brain Tumor Foundation Institute, and The Preston Robert Tisch Brain Tumor Center at Duke, Duke University Medical Center, Durham, North Carolina Corresponding Author: Hai Yan, Duke University Medical Center, Department of Pathology, DUMC-3156, 199B-MSRB, Research Drive, Durham, NC 27710. Phone: 919-668-7850; Fax: 919-684-8756; E-mail: hai.yan@dm.duke. edu doi: 10.1158/2159-8290.CD-12-0182 ©2012 American Association for Cancer Research. Management of the pediatric brain tumor medulloblastoma presents a signifi cant clinical dilemma. While aggressive therapeutic modalities result in tumor eradication in most standard risk cases, the extent of chemoand radiotherapy necessary to reliably prevent disease recurrence is devastating to the developing central nervous system. In addition, some aggressive subgroups of medulloblastoma are frequently refractory to treatment (1). The threat of such resistance and recurrence may well be attributed to brain tumor stem cells, which have been implicated in the recovery of tumor mass following radiation therapy (2). Refi nement in medulloblastoma treatment must then address the need to eliminate these resilient tumor cells that may not respond to therapies designed to target the tumor bulk. Ultimately, the discovery of vulnerabilities distinct to medulloblastoma stem cells could permit the selective destruction of the tumor while sparing the developing central nervous system. Presently, the mechanisms of cancer stem cell–mediated tumor maintenance and propagation are poorly understood. The dynamic phenotype and, in most cases, the rarity of cancer stem cells complicate their prospective enrichment for functional or comparative studies. This is generally overcome by either selecting for unique stem cell characteristics in vitro or sorting for cells that express particular surface markers that associate with tumor-propagating activity. In this issue of Cancer Discovery, Corno and colleagues (3) enriched normal and tumor stem cell populations by culturing under neurosphere assay conditions to compare the transcriptomes of tumor stem cells isolated from medulloblastomas of the Ptch+/− mouse strain and normal neural stem cells. With this approach, the extent of similarity between normal and tumor stem cells could be determined, and ultimately a gene expression signature distinctly associated with tumorigenic stem cells was identifi ed. These fi ndings reveal unexpected similarities between medulloblastoma stem IN THE SPOTLIGHT Apples to Origins: Identifying Brain Tumor Stem Cell Genes by Comparing Transcriptomes of Normal and Cancer Stem Cells Matthew Wortham and Hai Yan Summary: The mechanisms whereby medulloblastoma stem cells coordinate tumor propagation are poorly understood. Using microarray analysis, Corno and colleagues draw parallels and distinctions between medulloblastoma stem cells from the Ptch+/− mouse and normal neural stem cells, identifying Ebf3 as a cancer stem cell–specifi c transcript critical for tumor growth. Cancer Discov; 2(6); 492–4. ©2012 AACR.