Editor—The APC tumour suppressor gene contains at least 21 exons, including four exons upstream of exon 1.1 2 Alternative splicing involves at least seven exons, including the first five exons, and creates distinct splice forms of APC RNA.1-4Exon 1 contains an in frame stop codon upstream of its initiating methionine; hence only splice forms of APCthat lack exon 1 allow exons 5′ of exon 1 to be translated. Interestingly, splice forms lacking exon 1 are enriched in terminally differentiated tissues including brain,5 intimating that protein isoforms containing domains encoded by the exons 5′ to exon 1 may be important in cellular differentiation. This study evaluates neurones and glia of the rodent nervous system and asks which cell types express APC isoforms lacking exon 1.

Medulloblastomas and glioblastomas are neuroepithelial tumours derived from neuronal progenitor cells and glial cells, respectively.6 7 Both tumour types occur at increased frequency in a subset of adenomatous polyposis coli (APC) patients8; APC patients developing these tumour types have a variant of APC known as Turbot's syndrome.9 APC is an autosomal dominant disorder caused by the inactivation of one copy of the APC gene.10 11APC patients develop hundreds to thousands of adenomatous polyps and if the colon is not removed, colon carcinoma develops.8 The relative risk of brain tumour formation is 23 times greater for APC patients when compared to the general population between the ages of 0 and 29.12 This study also examines the genetic basis of neuroepithelial tumour formation and examinesAPC as a mutational target in medulloblastomas and glioblastomas. We assayed 41 sporadic glioblastomas and medulloblastomas, five cell lines derived from neuroepithelial tumour types, and one medulloblastoma from an APC patient to examine the possibility that mutations in …