AXIN1 mutations but not deletions in cerebellar medulloblastomas

Medulloblastoma is a malignant, invasive embryonal tumour of the cerebellum which manifests preferentially in children. A subset of cases is associated with colon cancer and APC germline mutations (Turcot syndrome), and APC and beta-catenin point mutations occur in up to 10% of sporadic cases, indicating the involvement of the Wnt pathway in the development of medulloblastoma. In 39 sporadic cerebellar medulloblastomas screeened for alterations in the AXIN1 gene, another component of the Wnt pathway, we found missense AXIN1 mutations in two tumours, CCC --> TCC at codon 255 (exon 1, Pro --> Ser) and TCT --> TGT at codon 263 (exon 1, Ser --> Cys). Furthermore, the A allele at the G/A polymorphism at nucleotide 16 in intron 4 was significantly over-represented in medulloblastomas (39 cases; G 0.76 vs-A 0.24) compared to healthy individuals (86 cases; G 0.91 vs A 0.09; P = 0.0027). RT-PCR revealed large deletions in the AXIN1 gene in 5/12 (42%) medulloblastomas, consistent with a previous report. However, we observed such deletions at a similar frequency also in normal brain tissue (6/12, 50%). Since there are multiple complementary, inverted sequences present in the AXIN1 gene, these large deletions may represent RT-PCR errors due to stem-loop secondary structures.