ANALYSIS OF CHROMOSOME-22 LOCI IN MENINGIOMA - ALTERATIONS IN THE LEUKEMIA INHIBITORY FACTOR (LIF) LOCUS

Meningiomas are typically benign tumors arising from arachnoidal cells at the base of the brain. Meningioma is thought to result from the lo ss or inactivation of a putative tumor suppressor gene located on chro mosome 22. We analyzed a set of meningioma DNA specimens by Southern b lot hybridization with chromosome 22-specific probes and by PCR using oligomer primers and probes specific to the leukemia inhibitory factor (LIF) gene. Southern analysis suggested that a subset of our specimen s are monosomic for 22q11-qter and may have lost one entire copy of ch romosome 22. The gene(s) involved in the etiology of meningioma has be en localized to 22q11.2-12.3. The locus encoding LIF, a factor that af fects the differentiation and proliferation of numerous cell types, ha s also been localized to this region, at 22q12.1-12.2. The partial ove rlap of these loci, coupled with the known involvement of the LIF gene product in growth and differentiation, suggested that the LIF locus m ay be associated with the meningioma defect. We have examined the LIF locus in meningioma specimens at the molecular level by PCR, and by DN A and RNA gel-blot hybridizations. Alterations in the structure and/or expression of the LIF locus were detected in several specimens, inclu ding the subset that were shown to be monosomic for 22q. All of our tu mor specimens were shown to be undermethylated at the LIF locus relati ve to constitutional DNA from the same patients Sequence analysis of L IF cDNA from a meningioma revealed the existence of a novel, alternati vely spliced LIF mRNA. These results suggest that the LIF gene may be near the putative tumor suppressor locus associated with the developme nt of this phenotype.