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Deletions involving regions of chromosome 10 occur in the vast majority (> 90%) of human glioblastoma multiformes. A region at chromosome 10q23-24 was implicated to contain a tumour suppressor gene and the identification of homozygous deletions in four glioma cell lines further refined the location. We have identified a gene, designated MMAC1, that spans these deletions and encodes a widely expressed 5.5-kb mRNA. The predicted MMAC1 protein contains sequence motifs with significant homology to the catalytic domain of protein phosphatases and to the cytoskeletal proteins, tensin and auxilin. MMAC1 coding-region mutations were observed in a number of glioma, prostate, kidney and breast carcinoma cell lines or tumour specimens. Our results identify a strong candidate tumour suppressor gene at chromosome 10q23.3, whose loss of function appears to be associated with the oncogenesis of multiple human cancers.

The elevated plus maze is a widely used behavioral assay for rodents and it has been validated to assess the anti-anxiety effects of pharmacological agents and steroid hormones, and to define brain regions and mechanisms underlying anxiety-related behavior. Briefly, rats or mice are placed at the junction of the four arms of the maze, facing an open arm, and entries/duration in each arm are recorded by a video-tracking system and observer simultaneously for 5 min. Other ethological parameters (i.e., rears, head dips and stretchedattend postures) can also be observed. An increase in open arm activity (duration and/or entries) reflects anti-anxiety behavior. In our laboratory, rats or mice are exposed to the plus maze on one occasion; thus, results can be obtained in 5 min per rodent. INTRODUCTIONThe elevated plus maze has been described as a simple method for assessing anxiety responses of rodents by File and co-workers 1 . A task, using a Y-shaped apparatus that included an elevated open alley, which produced a strong approach-avoidance conflict, and an enclosed alley, which did not, was first described by Montgomery 2 . This task was modified into an elevated maze with four arms (two open and two enclosed) that are arranged to form a plus shape and was described by Handley and Mithani 3 . These authors described the assessment of anxiety behavior of rodents by using the ratio of time spent on the open arms to the time spent on the closed arms. Unlike other behavioral assays used to assess anxiety responses that rely upon the presentation of noxious stimuli (i.e., electric shock, food/water deprivation, loud noises, exposure to predator odor, etc.) that typically produce a conditioned response, the elevated plus maze relies upon rodents' proclivity toward dark, enclosed spaces (approach) and an unconditioned fear of heights/open spaces (avoidance) 4 .There is great diversity in possible applications of the elevated plus maze. To name a few, prescreening of newly developed pharmacological agents for treatment of anxiety-related disorders can be carried out. The anxiolytic and anxiogenic effects of pharmacological agents, drugs of abuse and hormones can be investigated. The effects of reproductive senescence/aging and/or pre-, peri-or postnatal exposure to various stressors can be assessed. Furthermore, beyond its utility as a model to detect anxiolytic effects of benzodiazepine-related compounds, the elevated plus maze can be used as a behavioral assay to study the brain sites (e.g., limbic regions, hippocampus, amygdala, dorsal raphe nucleus, etc. 5,6 ) and mechanisms (e.g., GABA, glutamate, serotonin, hypothalamic-pituitary-adrenal axis neuromodulators, etc. 1,3,[7][8][9][10][11][12] ) underlying anxiety behavior. Indeed, the elevated plus maze has been used as a model of state, unconditioned anxiety for over two decades, and there are now over 2,000 papers related to this topic. Because a lengthy discussion of these key findings is beyond the scope of this protocol, readers are referred to several excellent an...

Loss of heterozygosity data from familial tumors suggest that BRCA1, a gene that confers susceptibility to ovarian and early-onset breast cancer, encodes a tumor suppressor. The BRCA1 region is also subject to allelic loss in sporadic breast and ovarian cancers, an indication that BRCA1 mutations may occur somatically in these tumors. The BRCA1 coding region was examined for mutations in primary breast and ovarian tumors that show allele loss at the BRCA1 locus. Mutations were detected in 3 of 32 breast and 1 of 12 ovarian carcinomas; all four mutations were germline alterations and occurred in early-onset cancers. These results suggest that mutation of BRCA1 may not be critical in the development of the majority of breast and ovarian cancers that arise in the absence of a mutant germline allele.