PTEN

About PTEN

PTEN on chromosome 10q23.31 encodes phosphatase and tensin homolog, a lipid phosphatase that converts PIP3 back to PIP2, opposing PI3K and restraining the PI3K, AKT, and mTOR growth signaling pathway. It was identified in 1997 and is one of the most frequently inactivated tumor suppressors in cancer, commonly lost in glioblastoma, prostate, endometrial, breast, and other cancers. Germline PTEN variants cause PTEN hamartoma tumor syndrome, an umbrella term that includes Cowden syndrome and Bannayan Riley Ruvalcaba syndrome. Cowden syndrome is characterized by multiple hamartomas, macrocephaly, characteristic skin lesions such as trichilemmomas, and increased lifetime risks of breast, thyroid, endometrial, kidney, and colorectal cancers. Bannayan Riley Ruvalcaba syndrome involves macrocephaly, developmental delay, lipomas, and pigmented spots on the penis. A notable fraction of children with autism spectrum disorder and very large head size carry germline PTEN variants. PTEN also regulates cell migration and genomic stability. Because PTEN loss activates mTOR, mTOR inhibitors such as sirolimus have been studied for some manifestations, and inhibitors of PI3K and AKT are being developed for PTEN deficient tumors.