N Engl J Med: PTEN gene inactivation leads to cancer

June 3, 2020 /
an international team of researchers led by the Cleveland Clinic found that patients without the PTEN gene mutation may still experience a high cancer risk associated with PTEN tumor syndrome (The PTEN tumoroma, PHTS)in a new study published in New England Journal of Medicine,team led by Charis Eng, M.D., of the Institute of Genomic Medicine at the Cleveland Clinic, and Pier Paolo Pandolfi, M.D., of the University of Turin, Italy, found that mutations in the gene WWPI may be an additional genetic factor in PHTS-related cancersOverall, PHTS refers to a range ofgeneticdiseases that carry the reproductive PTEN mutation, which increase the risk of benign growth and tumors, cognitive and behavioral impairments, giant malformations, and certain cancersAlthough the embryo mutation of thetumorinhibiting gene PTEN is the cause of the determined PHTS, about 75% of individuals with typical clinical characteristics have been found to not carry PTEN mutations (called "wild type")image source: https://cn.bing.com
"Our results suggest that in patients we see without the PTEN gene mutation, the WWPI gene mutation may account for at least some of the reasons," DrEng said"It is important that, unlike PTEN, the fact that WWPI and its regulated cellular pathways are drug-enabled targets is important for cancer prevention and treatment and could open the door to future drug development research." "
in this study, researchers analyzed wWP1 variants in a group of PTEN wild patients because previous studies have found that enzymes encoded by WWPI can be overexpressed and/or amplified in multiple types of cancers, inhibiting PTEN function and causing growth in tumors in experimental models they found these mutations in a population with a family history of abnormal growth of colon and rectal walls, and expanded analysis of patients who had no prior analysis found that The WWP1 reproductive system mutated in 4% of PTEN wild patients with gastrointestinal oligopolyposis as the main clinical feature This is important because the phenomenon of oligopoly has long avoided causation In addition, the researchers found that the reproductive cell line WWP1 variant was significantly enriched in patients affected by the release of cancer, including phTS-related cancer types, particularly colorectal adenocarcinoma and thyroid cancer at the institutional level, they found that in experimental models, certain WWP1 variants caused abnormal activation of The WPP1 enzyme, inhibited PTEN function, and ultimately led to cancer development and progression by increasing the of tumors More research is needed, but the researchers concluded that the Reproductive Cell Line WWP1 variant in PTEN wild patients may benefit from prevention and/or treatment measures to regulate the WWP1-PTEN axis "These findings are very exciting because they relate to the causes of WWP1 somatic cell cancers in a variety of tissues, suggesting cancer susceptibility and have important prognosis and therapeutic value," said Dr Pandolfi, Because these enzymes are existing drugs that can be targeted for treatment "
Eng is the first president of the Institute of Genomic Medicine and director of the Personalized Genetic Health Center She is a professor of cancer genetic medicine for Sondra J and Stephen R Hardis Dr Pandolfi is a professor of cancer biology and genetic at the University of Turin and Harvard Medical School this study is supported in part by the National Institutes of Health, the National Cancer Institute, the American Cancer Society's Professor of Clinical Research, the Breast Cancer Research Foundation, and the Doris Duke Award for Outstanding Clinical Scientists (biovalleybioon.com) Reference: Gene inactivation of PTEN drives prelyn
Yu-Ru Lee et al.
WWP1 Gain-of-Functionactivation Inactive in-of-PTEN In Cancer Pre List of the N Engl J Med 2020; 382:2103-2116 DOI: 10.1056/NEJMoa1914919