This is the first report of Cowden syndrome presenting with ovarian dysgerminoma, which implicates PTEN in the molecular pathogenesis of dysgerminoma and adds it to the phenotypic manifestations of Cowden syndrome.
Large rearrangements of the PTEN gene can be involved as causing mutation in Cowden disease and MAPH is an efficient screening methodology to detect such a genetic alteration.
Of the four, three had deletions stretching to exon 1, but not 3' of it; importantly, one classic CS patient harbored a germline deletion localizing to this E-box region, further affirming the role of this element in PTEN's regulation and deregulation, and its contribution to the pathogenesis of CS.
Furthermore, we review the PTEN mutation positive BRRS cases, to further delineate the phenotype and to compare the cases with a genomic deletion with the cases with a point mutation.
These results indicate that the germline mutation of the PTEN gene and the consequent loss of heterozygous expression may lead to an increase in the survival potential of cells, thereby elucidating a role of PTEN in the pathogenesis of tumor generation and hyperplasia of lymphoid tissue in CD.