Genetic alterations in adult diffuse glioma: Occurrence, significance, andprognostic implications

Our understanding of diffuse glioma development and progression has expande d remarkably over the past decade. As the genetic alterations responsible f or these tumors are identified, molecular models of glioma pathogenesis are emerging and hold great promise to explain the biologic mechanisms of thes e neoplasms. Although these models continue to evolve and remain highly sim plified, some of the genetic alterations that they encompass appear to be p rognostically useful. Among the astrocytic gliomas, age and tumor grade are the most powerful indicators of patient survival, however, a wide range of variability remains, particularly among the low-grade and anaplastic astro cytomas. Recent reports indicate that alterations of the PTEN tumor suppres sor gene are independent predictors of overall survival for anaplastic astr ocytoma patients, helping to distinguish the cases with behavior resembling their more malignant counterparts, the glioblastomas. Among the oligodendr oglial tumors, alterations of the 1p and 19q chromosome arms have emerged a s potentially powerful predictors of overall patient survival and in vivo c hemotherapeutic response, while alterations of the p16/CDKN2A tumor suppres sor gene suggest shorter overall survival. As our molecular models continue to improve, through functional analyses and the identification of addition al genetic contributors, we will expand our capacity to more effectively pr ognose these patients and to design rational therapeutic strategies.