Allelic losses and prognosis in meningiomas

Background and Proposal: An association of complex tumor karyotype with aggressive behaviour has been previously observed in meningiomas. At molecular level, inactivation of a Tumor Suppressor Gene (TSG) located in #22 is considered at present as the first step for the development of a meningioma. The addition of inactivations of putative TSGs located in other chromosomes, not yet well defined, could act as subsequent events for genetic evolution and biological progression in these tumors. To approach this problem, correlations among LOH analysis results and the observation of aggressive behaviour criteria have been studied in a series of meningiomas. Methods: Pathological grading and recurrent character after long term follow up range 3-7 years) have been reviewed in a series of 58 meningiomas, and correlated with LOH analysis of alleles for markers on chromosomes #22, #1 and #14 loci, performed in tumor samples after resection. Molecular methods and results have already been reported elsewhere in detail by the same group. For statistical analysis of correlations, fisherʹs and X2 tests have been applied. Results: Aggressive criteria -atypical pathological features and/or recurrent character- were present in tumors Normal (N) for the alleles studied, in meningiomas with LOH only for #22 (−22), in samples with LOH for #22 and #1, independently of the #14 status (−22, −1), in tumors with LOH for #22 and #14 not considering #1 status (−22, −14), in with LOH only for #1 and/or #14 (OM), and in tumors showing LOH simultaneously for alleles at #22, #1 and #14 (−22, −1, −14). The associations had levels of significance (p < 0.05) when comparing either (−22, −1) or (−22, −14) groups against N or −22 groups, and p < 0.01 when comparing (−22, −1, −14) versus N or −22 groups. Conclusion: These results support an additive and sequential effect of allelic losses, at #1 and #14 loci, to the inactivation of TSG on #22 for the biological progression to an aggressive character, with bad prognosis, in meningiomas.