PTEN and retinoblastoma: Other alterations frequently observed in aggressive forms include the loss or mutation of tumor suppressor genes [20], such as BRCA1/BRCA2 (breast cancer), PTEN (phosphatase and tensin homolog), p53 and RB (retinoblastoma), and the activation of PI3K/Akt pathway that promote proliferation and reduce sensitivity to apoptotic stimuli.