EVIDENCE FOR CLONAL ORIGIN OF NEOPLASTIC NEURONAL AND GLIAL-CELLS IN GANGLIOGLIOMAS

Gangliogliomas are rare tumors of the central nervous system that acco unt for approximately 1% of all brain tumors. Histologically, gangliog liomas are composed of intimately admired glial and neuronal component s, the pathological origins of which remain to be characterized. Clona l analysis through examination of the pattern of the X chromosome inac tivation allows one to distinguish monoclonal differentiation of a gen etically abnormal progenitor cell from parallel, but independent, clon al expansion of two different cell types during tumorigenesis in bipha sic neoplasms, such as gangliogliomas. In the present study, we invest igated the clonality of eight gangliogliomas from female patients usin g both methylation- and transcription-based clonality assays at the an drogen receptor locus (HUMARA) on the X chromosome. Among tumors from seven patients who were heterozygous at the HUMARA locus, five were id entified as monoclonal with the methylation-based clonality assay, and the results were confirmed by the transcription-based method, whereas two were shown to be polyclonal by the methylation-based clonality as say but monoclonal by transcription-based clonality analysis. We concl ude that the predominant cell types in most gangliogliomas are monoclo nal in origin and derive from a common precursor cell that subsequentl y differentiates to form neoplastic glial and neuronal elements.