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Allelic loss of 17p13.3 is observed in approximately 40% of medulloblastomas, suggesting the presence of a tumor suppressor gene in this region. Deletion mapping has defined a region of common loss flanking the telomeric marker D17S34, and a recent report delineated a 9-kb homozygous deletion within the D17S34 locus in one such tumor. Using cDNA selection, we have identified a transcript spanning this deletion, designated (HSA)RPH3AL (rabphillin-3A-like), based on its 77% overall amino acid identity with a recently cloned rat gene, (RNO)Rph3al (originally termed Noc2), a gene putatively involved in regulated endocrine exocytosis through its interactions with the cytoskeleton. We determined the exon-intron boundaries of RPH3AL and screened the coding region for mutations by direct sequencing in DNA extracted from 33 tumor samples with allelic loss of 17p13, including 10 medulloblastoma, 14 follicular thyroid cancer (FTC), and 9 ovarian cancer specimens. No mutations were identified. Thus, despite its location in a homozygously deleted 17p13.3 locus, it is unlikely that RPH3AL is a gene involved in the oncogenesis of medulloblastoma, FTC, or ovarian cancer., (Copyright 1999 Academic Press.)

The beta-catenin, glycogen synthase kinase 3beta (GSK-3beta), and adenomatous polyposis coli (APC) gene products interact to form a network that influences the rate of cell proliferation. Medulloblastoma occurs as part of Turcot's syndrome, and patients with Turcot's who develop medulloblastomas have been shown to harbor germ-line APC mutations. Although APC mutations have been investigated and not identified in sporadic medulloblastomas, the status of the beta-catenin and GSK-3beta genes has not been evaluated in this tumor. Here we show that 3 of 67 medulloblastomas harbor beta-catenin mutations, each of which converts a GSK-3beta phosphorylation site from serine to cysteine. The beta-catenin mutation seen in the tumors was not present in matched constitutional DNA in the two cases where matched DNA was available. A loss of heterozygosity analysis of 32 medulloblastomas with paired normal DNA samples was performed with four microsatellite markers flanking the GSK-3beta locus; loss of heterozygosity with at least one marker was identified in 7 tumors. Sequencing of the remaining GSK-3beta allele in these cases failed to identify any mutations. Taken together, these data suggest that activating mutations in the beta-catenin gene may be involved in the development of a subset of medulloblastomas. The GSK-3beta gene does not appear to be a target for inactivation in this tumor.

There was a drop of 56% in the hypothalamic content of Gn-RH in female voles 5 min after mating compared with that in unmated but receptive animals. This suggests that the surge of LH in vole plasma associated with reflex ovulation is evoked by a massive release of Gn-RH.

1. Previous studies on the effect of preoptic and median eminence stimulation on the immunoreactive LRF content of pituitary stalk blood from pro-oestrous rats have been extended. Stimulation of the suprachiasmatic nuclei and anterior hypothalamic area produced increments in LRF which were 66 and 18% respectively, of that produced by preoptic stimulation, and 38 and 9%, respectively, of that produced by stimulation of the median emience. Stimulation of the amygdala and hippocampus had no effect. 2. The LRF response was not affected significantly when preoptic stimulation was accompanied by stimulation of the hippocampus. 3. In animals subjected to section of the dorsal afferents of the diencephalon, the LRF response to preoptic stimulation was similar to that in intact rats. However, the facilitatory effect of oestrogen on the LRF response to preoptic stimulation was significantly reduced in the roof sectioned compared with intact animals. The post-operative resumption of oestrous cycles was delayed but not abolished by dorsal deafferentation.