Cowden disease (CD) is an autosomal dominant cancer predisposition syndrome associated with an elevated risk for tumours of the breast, thyroid and skin. Lhermitte-Duclos disease (LDD) cosegregates with a subset of CD families and is associated with macrocephaly, ataxia and dysplastic cerebellar gangliocytomatosis. The common feature of these diseases is a predisposition to hamartomas, benign tumours containing differentiated but disorganized cells indigenous to the tissue of origin. Linkage analysis has determined that a single locus within chromosome 10q23 is likely to be responsible for both of these diseases. A candidate tumour suppressor gene (PTEN) within this region is mutated in sporadic brain, breast and prostate cancer. Another group has independently isolated the same gene, termed MMAC1, and also found somatic mutations throughout the gene in advanced sporadic cancers. Mutational analysis of PTEN in CD kindreds has identified germline mutations in four of five families. We found nonsense and missense mutations that are predicted to disrupt the protein tyrosine/dual-specificity phosphatase domain of this gene. Thus, PTEN appears to behave as a tumour suppressor gene in the germline. Our data also imply that PTEN may play a role in organizing the relationship of different cell types within an organ during development.
Two major groups of respiratory syncytial virus (RSV) strains, A and B, have been identified and their patterns of isolation determined in different communities but not simultaneously in multiple communities. In this study, we tested 483 RSV isolates from 14 university laboratories in the United States and Canada for the 1984/1985 and 1985/1986 RSV seasons; 303 (63%) isolates were group A, 114 (24%) were group B, and 66 (14%) could not be grouped. Isolates were subdivided into six subgroups within group A and three within group B; up to six and often four or more different subgroups were isolated in the same laboratory during the same RSV season. The pattern of group and subgroup isolations varied among laboratories during the same year and between years for the same laboratory. These differences suggest that RSV outbreaks are community, possibly regional, but not national phenomena. The ability to identify group and subgroup differences in isolates is a powerful tool for epidemiologic studies of RSV.
