Deletions of AXIN1, a component of the WNT/wingless pathway, in sporadic medulloblastomas

Medulloblastoma (MB.) represents the most frequent malignant brain tumor in children. Most MBs appear sporadically; however, their incidence is highly elevated in two inherited tumor predisposition syndromes, Gorlin's and Tur cot's syndrome. The genetic defects responsible for these diseases have bee n identified. Whereas Gorlin's syndrome patients carry germ-line mutations in the patched (PTCH) gene, Turcot's syndrome patients with MBs carry germ- line mutations of the adenomatous polyposis coli (APC) gene. The APC gene p roduct is a component of a multiprotein complex controlling beta -catenin d egradation. In this complex, Axin plays a major role as scaffold protein. W hereas A-PC mutations are rare in sporadic MBs, a hot-spot region of beta - catenin (CTNNB1) mutations was identified in a subset of MBs. To find out i f Axin is also involved in the pathogenesis of sporadic MBs, we analyzed 86 MBs and 11 MB cell lines for mutations in the AXIN1 gene. Using single-str and conformation polymorphism analysis, screening for large deletions by re verse transcription-PCR, and sequencing analysis, a single somatic point mu tation in exon 1 (Pro255Ser) and seven large deletions (12%) of AXIN1 were detected. This indicates that AXIN1 may function as a tumor suppressor gene in MBs.