Localization of the Bannayan-Riley-Ruvalcaba syndrome gene to chromosome 10q23

PTEN, a unique tumor suppressor gene.

“…It has also been suspected to be the site for loci associated with certain inherited disorders such as hamartomatous syndromes (Nelen et al 1996, Jacoby et al 1997, Zigman et al 1997. This group of diseases includes Cowden syndrome (CS), an autosomal dominant disorder which comprises multiple hamartomas in tissues derived from the three major embryological layers, and is associated with a higher risk of breast and follicular or papillary thyroid cancer (25-50% of affected females, and 10% of affected individuals respectively), and in a subset of cases, a dysplatic ganglyocytoma of the cerebellum, Lhermitte-Duclos disease, might also develop.…”

Polyps as biomarkers for colorectal neoplasia

“…The findings of genetic markers specific for hamartomatous polyps of the familial syndromes of juvenile polyposis (12)(13)(14)(15) and Peutz Jegher Syndromes (16), conditions associated with considerable CRC risk, suggests that other complementary pathways exist through which neoplasia may progress. The genetic aberrations in these syndromes abide not in the epithelial component, but in the mesenchymal tissue, suggesting some biochemical "crosstalk" between the epithelial component and the matrix (17,18), long-recognized but heretofore ill-defined.…”

“…There is an increased incidence of CRC among relatives of patients with this condition and this is not seen in the nonfamilial variant, where affected individuals have also been described to have developed CRC. Recently 2 groups have described a somatic mutation on chromosome 10q in patients with the familial form (12,13). In situ hybridization revealed that the mutation resides in the mesenchymal elements rather than in the ectodermally derived epithelial cells.…”

“…However, the number of polyps that develop depend on the genetic makeup of the mouse and is thought to be governed by a modifier of Min (MOM-1) which is an unlinked modifier of polyp multiplicity and growth (13). The candidate for this mouse model resides on mouse chromosome 4 and encodes a secretory phospholipase (Pla2a) which when overexpressed using a cosmid transgene, caused a decrease in adenoma number and size (89).…”

Cowden-Syndrom (Multiples Hamartom-Syndrom)

“…Ein Verlust der PTEN−Genfunktion kann bei vielen menschlichen Karzinomar− ten gefunden werden [21]. Derselbe Defekt liegt auch bei der ju− venilen Polyposis des Darms und beim Bannayan−Riley−Ruvalca− ba−Syndrom vor, einer ebenfalls autosomal−dominant vererbten Genodermatose [20,22]. Das Cowden−Syndrom und das Banna− yan−Riley−Ruvalcaba−Syndrom weisen eine teilweise überlap− pende Symptomatik auf: Die klassischen Triade des Bannayan− Riley−Ruvalcaba−Syndroms besteht aus Makrozephalie, genitaler Lentiginose und ± analog zum Cowden−Syndrom ± intestinaler Polyposis [23].…”