Identification of new members of the Gas2 and Ras families in the 22q12 chromosome region.

Monitoring of loss of heterozygosity in human tumors has suggested that the 22q12 region may contain another tumor suppressor gene(s) in addition to the NF2 gene. The genomic sequencing of a 40-kb region bounded by the EWS and BAM22 genes and containing a CpG-rich region has identified two new genes in the q12 region of chromosome 22. One of them, GAR22, is closely related to mouse Gas2, a gene isolated as being negatively regulated by serum and growth factors and exhibiting a high expression in growth arrested mouse fibroblasts. The other, RRP22, belongs to the Ras superfamily, in which it defines a new subgroup. Its expression appears to be strictly limited to the central nervous system. Growth-arrest-specific and Ras-related genes are likely candidates to be involved in tumorigenic processes. Although no mutation was observed in a small set of meningiomas and schwannomas, alteration of these new genes should now be searched in other tumors with frequent allelic losses on chromosome 22 not associated with NF2 mutation.