NONISOTOPIC MOLECULAR CYTOGENETICS IN NEUROONCOLOGY

The molecular genetic analysis of brain tumours has been the focus of considerable interest for a number of years. However, these studies ha ve been largely directed towards understanding the fundamental biologi cal processes involved in tumorigenesis and the techniques which have been used require considerable molecular biological skills. Unfortunat ely, there has not been the impetus to correlate basic biological stud ies with clinical or neuropathological features. The development of no nisotopic molecular cytogenetic in situ hybridization (ISH) techniques which can be applied to archival tumour material provides an opportun ity to address a wide range of neuropathological questions at a geneti c level. Identification of specific chromosomes has been made possible by the isolation of probes which recognize the highly repeated sequen ces present in the centromeric regions of individual chromosomes. Libr aries of human chromosome-specific painting probes are also available. A range of probes which bind to the whole or part of specific single copy genes are becoming available. These can be detected with either f luorochromes with different emission colours or with enzymatic detecti on systems in either interphase nuclei derived from fresh, fixed and e mbedded tumour samples, touch preparations or smears (so-called 'inter phase cytogenetics') as well as conventional metaphase spreads. Compar ative genomic hybridization can be used to scan the entire genome for deletions or amplifications without any pre-existing information about the likely locations of these abnormalities or the availability of an y specific DNA probes. These techniques can be used to identify aneupl oidy or structural alterations in individual chromosomes and are likel y to yield important information about the location of genes important in the pathogenesis of brain tumours and may also provide the basis f or the refinement of diagnostic or prognostic criteria of these neopla sms.