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Deletion of the q23-24 region of human chromosome 10 is one of the most frequent genetic alterations in prostate cancer, suggesting that inactivation of a tumor suppressor gene in this region is involved in the development or progression of this carcinoma. A candidate gene, PTEN/MMAC1, has been identified from this chromosomal region; mutations of this gene have been found in various advanced tumors and cell lines including those of prostate cancer. To further define the role of PTEN/MMAC1 in the development of prostate cancer and its spectrum of genetic alterations, we analysed 40 pT2 or pT3 prostate tumors for allelic loss, mutations, and homozygous deletions using PCR-based methods. Six tumors showed loss of heterozygosity for one of the ten markers analysed, while one tumor showed loss of two markers. None of the markers within PTEN/MMAC1 was lost. Direct sequencing of PCR amplified exons and intron/exon junctions of all 40 tumors revealed three sequence variants, one of which was a point mutation in exon 9, while the other two were polymorphisms. Using multiplex PCR, no homozygous deletions were detected in any of the neoplasms. Our results showing a low frequency of alterations of PTEN/MMAC1 in pT2 and pT3 prostate cancers suggest that this gene plays an insignificant role in the development of most low stage carcinomas of the prostate.

Sorex cinereus (masked shrew) and Sorex fumeus (smoky shrew) are syntopic species co-occurring in relict fragments of spruce–fir habitat on southern Appalachian mountaintops. We conducted phylogenetic and population genetic analyses of 20 high-elevation Sorex populations in 8 distinct boreal islands. Partial mitochondrial DNA sequences (cytochrome b and D-loop) were compared with amplified fragment length polymorphism markers obtained by restriction of whole genomic DNA. The 2 species, though similar in morphology and ecological niche, have dissimilar phylogeographic patterns. S. cinereus, despite its more limited present-day southern Appalachian range, exhibits markedly less population structure than S. fumeus. What structure is present among masked shrew populations is randomized geographically, in contrast to a distinct association between genetic partitioning and geographic location among smoky shrew populations. Disparity in post-Pleistocene population densities of these species might be implicated in the discrepant patterns of phylogeographic structuring evident in their genomes as a result of historical vicariance. Although the metapopulations of both species exhibit genetic signatures consistent with continuous historical expansion, we believe that a localized catastrophic event induced a severe genetic bottleneck in Sorex populations at Whitetop Mountain, Virginia. This study contributes to a better understanding of the repercussions of boreal habitat fragmentation on the population dynamics and genetic diversity of associated vertebrate species.