Genomic aberrations in pediatric gliomas and embryonal tumors.

The pathogenesis of pediatric central nervous system tumors is poorly understood. To increase knowledge about the genetic mechanisms underlying these tumors, we performed genome-wide screening of 17 pediatric gliomas and embryonal tumors combining G-band karyotyping and array comparative genomic hybridization (aCGH). G-banding revealed abnormal karyotypes in 56% of tumor samples (9 of 16; one failed in culture), whereas aCGH found copy number aberrations in all 13 tumors examined. Pilocytic astrocytomas (n = 3) showed normal karyotypes or nonrecurrent translocations by karyotyping but the well-established recurrent gain of 7q34 and 19p13.3 by aCGH. Our series included one anaplastic oligoastrocytoma, a tumor type not previously characterized genomically in children, and one anaplastic neuroepithelial tumor (probably an oligoastrocytoma); both showed loss of chromosome 14 by G-banding and structural aberrations of 6q and loss of 14q, 17p, and 22q by aCGH. Three of five supratentorial primitive neuroectodermal tumors showed aberrant karyotypes: two were near-diploid with mainly structural changes and one was near-triploid with several trisomies. aCGH confirmed these findings and revealed additional recurrent gains of 1q21-44 and losses of 3p21, 3q26, and 8p23. We describe cytogenetically for the first time a cribriform neuroepithelial tumor, a recently identified variant of atypical teratoid/rhabdoid tumor with a favorable prognosis, which showed loss of 1p33, 4q13.2, 10p12.31, 10q11.22, and 22q by aCGH. This study indicates the existence of distinct cytogenetic patterns in pediatric gliomas and embryonal tumors; however, further studies of these rare tumors using a multimodal approach are required before their true genomic aberration pattern can be finally established.

Paediatric brain tumours: an embryological perspective.

Primitive neuroectodermal tumours are amongst the most common paediatric tumours of the central nervous system. These tumours are composed of undifferentiated cells and a variable component of more differentiated cell types. Most analysis of these tumours has focused on molecules normally found in the differentiated cells or those found in all primitive neuronal precursors. In this article we describe recent advances in understanding of the molecular processes involved in normal neurogenesis. We discuss the relevance of these data to the biology of neuronal tumours and describe strategies we and others have adopted to investigate the usefulness of molecules found in undifferentiated neuronal tissues in understanding the events which underlie oncogenesis in this tumour type.

Prospective identification, isolation by flow cytometry, and in vivo self-renewal of multipotent mammalian neural crest stem cells.

Multipotent and self-renewing neural stem cells have been isolated in culture, but equivalent cells have not yet been prospectively identified in neural tissue. Using cell surface markers and flow cytometry, we have isolated neural crest stem cells (NCSCs) from mammalian fetal peripheral nerve. These cells are phenotypically and functionally indistinguishable from NCSCs previously isolated by culturing embryonic neural tube explants. Moreover, in vivo BrdU labeling indicates that these stem cells self-renew in vivo. NCSCs freshly isolated from nerve tissue can be directly transplanted in vivo, where they generate both neurons and glia. These data indicate that neural stem cells persist in peripheral nerve into late gestation by undergoing self-renewal. Such persistence may explain the origins of some PNS tumors in humans.