Disease relevance of Hamartoma Syndrome, Multiple

• RESULTS: Germline missense mutation at codon 289 (AAA to GAA, Lys to Glu) and deletion of the wild-type allele were detected in the polyps of 2 patients with Cowden disease in the same family [1].
• Inherited mutations in PTEN that are associated with breast cancer, cowden disease, and juvenile polyposis [2].
• Mutation spectrum and genotype-phenotype analyses in Cowden disease and Bannayan-Zonana syndrome, two hamartoma syndromes with germline PTEN mutation [3].
• BACKGROUND: Germ-line and sporadic mutations in the tumor suppressor gene PTEN (also known as MMAC or TEP1), which encodes a dual-specificity phosphatase, cause a variety of cancers such as Cowden disease, glioblastoma, endometrial carcinoma and prostatic cancer [4].
• Carney complex, Peutz-Jeghers syndrome, Cowden disease, and Bannayan-Zonana syndrome share cutaneous and endocrine manifestations, but not genetic loci [5].

High impact information on Hamartoma Syndrome, Multiple

• PTEN germline mutations are found in three related human autosomal dominant disorders, Cowden disease (CD), Lhermitte-Duclos disease (LDD) and Bannayan-Zonana syndrome (BZS), characterized by tumour susceptibility and developmental defects [6].
• BACKGROUND & AIMS: To understand the molecular etiology of Cowden disease-associated gastrointestinal polyps, we analyzed the mutational status of PTEN/MMAC1, a recently identified Cowden disease gene located at 10q23, in gastric hamartomas, colonic adenoma, and juvenile polyps of 3 patients with Cowden disease [1].
• Variant manifestation of Cowden disease in Japan: hamartomatous polyposis of the digestive tract with mutation of the PTEN gene [7].
• Cowden disease, also known as multiple hamartoma syndrome, is an autosomal dominant cancer syndrome with a high risk of breast and thyroid cancer [8].
• Additionally, germ-line mutations of PTEN/MMAC1 are responsible for several familial neoplastic disorders, including Cowden disease and Bannayan-Zonana syndrome [9].

Chemical compound and disease context of Hamartoma Syndrome, Multiple

• Here we report that a missense mutation in PTEN, PTEN-G129E, which is observed in two Cowden disease kindreds, specifically ablates the ability of PTEN to recognize inositol phospholipids as a substrate, suggesting that loss of the lipid phosphatase activity is responsible for the etiology of the disease [10].
• 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 [11].
• Cowden's disease (multiple hamartoma and neoplasia syndrome) treated with isotretinoin [12].
• PJS and CNC share manifestations with Cowden syndrome (or Cowden disease) (CS, OMIM#158350) and Bannayan-Riley-Ruvalcaba syndrome (BRR, OMIM#153480) [13].
• A diagnosis was made as a typical case of Cowden's disease according to the criteria proposed by Salem and Steck (J Am Acad Dermatol 8: 686, 1983) [14].

Biological context of Hamartoma Syndrome, Multiple

• 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 [1].
• Activation of a cryptic splice site of PTEN and loss of heterozygosity in benign skin lesions in Cowden disease [15].
• That patient was observed to have a deletion in the critical portion of Exon 5 of the PTEN gene, the gene associated with Cowden disease [16].
• We have studied up to 70 cases of sporadic colorectal cancer for allele loss at markers predominantly on the long arm of chromosome 10, including loci flanking the putative Cowden Disease/JP1 locus [17].
• BACKGROUND: In 1997, it was reported that a PTEN gene deletion, a common genetic mutation in Cowden's disease (CD), was identified in a patient with Bannayan-Riley-Ruvacalba (BRR), suggesting that the two diseases were allelic [18].

Anatomical context of Hamartoma Syndrome, Multiple

• Germ-line mutations in PTEN give rise to several related neoplastic disorders, including Cowden disease [10].
• 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 [19].

Gene context of Hamartoma Syndrome, Multiple

• The main susceptibility genes are BRCA1 and BRCA2, but others include Cowden's disease, Li Fraumeni syndrome and ataxia-telangiectasia [20].
• The gene for Cowden disease has recently been localized to chromosome 10q22-q23, and a juvenile polyposis locus, JP1, has been reported as mapping to the same location [17].
• Mutations in the human PTEN gene have been identified in a number of different tumour types, and in the hamartomatous polyposis syndromes Cowden disease and Bannayan-Zonana syndrome [21].
• Effect of Helicobacter pylori eradication on gastric hyperplastic polyposis in Cowden's disease [22].
• Adult-onset LDD is now considered pathognomonic for Cowden disease [23].

References