Constipation, polyps, or cancer? let PTEN predict your future

Abstract

The inherited hamartoma polyposis syndromes encompass several distinct clinical syndromes with different genetic bases, Cowden syndrome (CS), Bannayan-Riley-Ruvalcaba syndrome (BRRS), juvenile polyposis syndrome (JPS), and Peutz-Jeghers syndrome (PJS). Germline mutations in PTEN, encoding a tumor suppressor phosphatase on 10q23.3, is associated with 80% of CS and 60% of BRRS. JPS is caused by mutations in MADH4 and BMPR1A, encoding two members of the TGFB superfamily. Germline mutations in LKB1 (STK11) are associated with a subset of PJS. The number, distribution, and histologic type of polyps differ amongst these syndromes as do component cancer risks. While rare, usually asymptomatic, hamartomatous polyps are felt to be component to CS. Hamartomatous polyposis is usually prominent and symptomatic in BRRS. Polyposis, which can be quite symptomatic, is a cardinal component feature of PJS and JPS. Interestingly, glycogenic acanthosis of the esophagus is highly predictive of CS and the presence of PTEN mutation. PTEN mutation positive CS have been shown to be at increased risk of breast, thyroid, and endometrial cancer. PTEN mutation positive BRRS are at increased risk of at least breast cancer, possibly that of the thyroid as well. In contrast, JPS and PJS have increased risk of gastrointestinal cancers in particular. Thus, molecular-based diagnoses to differentiate each of these syndromes are important for medical management.

Proteus syndrome: An update

“…Thus, for all practical purposes, diagnostic congruence was 100% . Several authors have reported patients who were said to have ''Proteus syndrome'' with PTEN mutations Smith et al, 2002] and others have repeatedly stated that PTEN mutations are a cause of a subset of patients with ''Proteus syndrome'' Eng, 2003;Kirk et al, 2004].…”

Pten Deficiency Activates Distinct Downstream Signaling Pathways in a Tissue-Specific Manner

“…Pten heterozygous mice (Pten +/À ) develop a spectrum of neoplasias in organs, such as the breast, thyroid, endometrium, and prostate, which closely resembles the situation in humans with PTEN mutation (5,(8)(9)(10). Somatic PTEN mutations in humans occur with a wide distribution of frequencies in sporadic primary tumors, with the highest frequencies in endometrial carcinomas and glioblastoma (11). PTEN mutation is among the most common genetic alterations reported in human prostate cancers, with loss of heterozygosity (LOH) of PTEN found in 30% of primary prostate cancers (12)(13)(14) and 63% of metastatic prostate cancer tissue samples (6).…”

PTEN Hamartoma Tumour Syndrome:Gastrointestinal Manifestations ofTwo Cases Diagnosed in Singapore

“…Gastrointestinal polyposis [2][3][4][5][6][7][8][9][10][11][12] Glycogenic acanthosis [2,8,11,13] Intestinal hyperplasia 14…”

“…Loss of function of PTEN contributes to tumourigenesis-specifically, hamartoma formation [1]. Multiple systems are involved and patients often demonstrate a wide spectrum of manifestations and presentations, including complications of gastrointestinal hamartomas, mucocutaneous abnormalities and an increased cancer risk [2]. There remains limited literature on cases reported in Asia.…”