Cowden disease is a genetic disorder associated with a mutation of the PTEN gene and is known to be easily complicated by generalized vascular malformations and malignant tumors.
Along with previous reports, this case suggests that acral plexiform PENs may be an early, highly specific finding in CS and highlights the importance of screening these patients for PTEN mutation.
Germline mutations in PTEN can predispose people to Cowden syndrome (CS) and Bannayan-Ruvalcaba-Riley (BRR) syndrome, rare, autosomal dominantly inherited neoplastic disorders.
Due to the chromosome 10 deletion involving contiguous portions of BMPR1A and PTEN in our patient, he may be at risk for CS associated cancers and features, in addition to the polyps associated with JPS.
Here, we describe a novel PTEN splicing site mutation in a family with classical Cowden disease and we studied benign skin lesions typical for Cowden disease for loss of heterozygosity.
Phosphatase and tensin homolog (PTEN) hamartoma tumor syndrome (PHTS) encompasses several rare disorders linked to mutations of the PTEN gene, including Cowden disease (CD) and Bannayan-Riley-Ruvalcaba syndrome (BRRS).
A PTEN mutation, c.1003C>T p.(Arg335Ter), was subsequently identified as the cause of Cowden syndrome in another family member (a nephew) with dysplastic gangliocytoma of the cerebellum (Lhermitte-Duclos disease), and genetic testing in the proband's daughter indicated that he was an obligate carrier of the mutation.
Caveolin-1 is of particular functional interest because it has been shown to interact with PTEN, the tumor suppressor gene mutated in Cowden syndrome, an inherited multiple hamartoma syndrome that includes predisposition to FTC.
Germline mutations of PTEN give rise to Cowden Disease (CD), an autosomal dominantly-inherited cancer syndrome which predisposes to increased risk of developing breast and thyroid tumors.
The diagnosis of Cowden syndrome with PTEN gene mutation, linked to higher risk of neoplasia and occurrence of hamartomatous lesions characteristic of the Lhermitte-Duclos disease (LDD), was confirmed by genetic investigation.
MBC can be associated with mutations in hereditary cancer predisposition syndrome genes (i.e., BRCA2); however, no such association has been reported in patients with Cowden syndrome (involving the phosphatase and tensin homolog [PTEN] gene).
Management of women with breast cancer suspected of CS who test negative for germline PTEN mutations should be managed as per a mutation carrier if she meets CS diagnostic criteria, and should be offered enrollment in research to identify other predisposition genes.
This study is the first to show that the mutational abrogation of PTEN/MMAC1 plays a causal role in the genesis of gastrointestinal polyps in Cowden disease, providing molecular genetic evidence that colonic adenoma, juvenile polyp, and gastric hamartoma could be included in the manifestations of Cowden disease.
Germ-line mutations of PTEN cause Cowden's syndrome (CS), a multiple hamartoma condition resulting in increased susceptibility for the development of cancer.
We have shown that germline mutations of PTEN are present in individuals with two hamartoma syndromes: Cowden Syndrome, associated with a predisposition to breast and thyroid cancers, and Bannayan-Zonana syndrome.
In the present study, 20 hamartomas from 11 individuals belonging to ten unrelated families with CD have been examined for LOH of markers flanking and within PTEN/MMACI.