The M6P/IGF2-receptor gene shows allelic loss but is not mutated in ependymomas

Ependymal tumors are heterogeneous with regard to morphology, localization, age at manifestation, and prognosis. Spinal tumor location, which predominantly occurs in adults, is associated with a better prognosis than intracranial ependymomas, which represent the majority of childhood ependymomas. While spinal ependymomas are associated with allelic losses on chromosome 22q and mutations in the NF2 tumor suppressor gene, losses of 6q have frequently been observed in pediatric ependymomas.

The mannose 6-phosphate/insulin-like growth factor 2 receptor gene (M6P/IGF2R) gene is located at 6q26. It encodes a multifunctional receptor required for activation of the growth inhibitor TGFβ1, the degradation of the mitogen IGF-2 and the intracellular sorting of lysosomal enzymes. Inactivating mutations of the M6P/IGF2R have been identified in different epithelial neoplasms, including hepatocellular carcinoma and lung cancer, indicating its role as a tumor suppressor gene.

Allelotyping and SSCP analysis were used to examine a panel of 40 ependymomas (comprising 30 tumors of intracranial and 10 of spinal origin) for genetic alterations of the distal long arm of chromosome 6 and mutations in exons encoding functional domains of M6P/IGF2R (M6P binding sites, IGF-2 binding regions, IGF-2 binding enhancing region). LOH of 6q was present in up to 25% of ependymomas, without a preference for intracranial or spinal localization. Apart from constitutional polymorphisms, SSCP analysis did not reveal any somatic mutations in the M6P/IGF2R gene. Analysis of M6P/IGF2R mRNA expression by competitive RT-PCR excluded a transcriptional silencing in both, spinal and intracranial ependymomas. These data indicate that the chromosomal arm 6q harbors a putative ependymoma associated tumor suppressor other than the M6P/IGF2R gene.