We recently identified a novel homologue of the adenomatous polyposis coli (APC) tumor suppressor gene, APCL, whose abundant and specific expression in the central nervous system indicated an important role in neuronal proliferation and differentiation. To investigate possible involvement of APCL alterations in brain tumors, we first analyzed the expression of APCL mRNA in seven glioma tissues by semi-quantitative reverse transcription polymerase chain reaction (RT-PCR) analysis, and in nine glioma cell lines by northern blotting. APCL expression was reduced significantly in most of the glioma tissues and all nine cell lines in comparison with normal brain tissue. However, single-strand conformation polymorphism (SSCP) analysis and DNA sequencing of the entire coding region of APCL detected no mutations in any of the glioma cell lines, or in any of the 35 astrocytic gliomas and five medulloblastomas examined. Our results suggested that some epigenetic mechanism is responsible for the decrease in APCL expression in our panel of brain tumors.