Trapping the mouse genome to hunt human alterations

摘要

Glioblastoma multiforme (GBM) are the most common and aggressive adult primary brain tumors. Genetic alterations and their consequences in these malignant astrocytomas have been studied extensively and include (ⅰ) overexpression of growth factors and their corresponding receptors (fibroblast growth factor, epidermal growth factor, and platelet-derived growth factors), (ⅱ) abnormalities of transduction signaling pathways (activation of PI3 kinase/AKT, RAS/MAP kinase, and protein kinase C), or (ⅲ) disruption of cell cycle arrest (loss of p16INK4A and pl4ARF, mutations in p53 protein, and PTEN). Whether these modifications are causative or participate in tumor progression is a pivotal question that can best be answered by modeling glioma formation in mice. In this issue of PNAS, Kamnasaran et al. combine genetically engineered murine (GEM) models of gliomas with a retroviral gene-trapping approach to identify new molecular alterations in human gliomas.