The phosphatase and tensin homolog deleted on chromosome 10 (PTEN) tumor 
suppressor is a phosphatase that antagonizes the phosphoinositol-3-kinase/AKT 
signaling pathway and suppresses cell survival as well as cell proliferation. 
PTEN is the second most frequently mutated gene in human cancer after p53. 
Germline mutations of PTEN have been found in cancer susceptibility syndromes, 
such as Cowden syndrome, in which over 80% of patients have mutations of PTEN. 
Homozygous deletion of Pten causes embryonic lethality, suggesting that PTEN is 
essential for embryonic development. Mice heterozygous for Pten develop 
spontaneous tumors in a variety of organs comparable with the spectrum of its 
mutations in human cancer. The mechanisms of PTEN functions in tumor suppression 
are currently under intense investigation. Recent studies demonstrate that PTEN 
plays an essential role in the maintenance of chromosomal stability and that 
loss of PTEN leads to massive alterations of chromosomes. The tumor suppressor 
p53 is known as a guardian of the genome that mediates the cellular response to 
environmental stress, leading to cell cycle arrest or cell death. Through 
completely different mechanisms, PTEN also protects the genome from instability. 
Thus, we propose that PTEN is a new guardian of the genome. In this review, we 
will discuss new discoveries on the role of PTEN in tumor suppression and 
explore mechanisms by which PTEN maintains genomic stability.