PTEN and neoplasm: This “canonical” O2-dependent regulatory system can be bypassed or disrupted by gain of oncogene function or loss-of-function mutations in tumor-suppressor genes (i.e. phosphatase and tensin homolog (PTEN)), or epigenetic silencing of the O2-sensing pathways resulting in constitutive O2-independent stabilization and expression of the HIFα-subunits which can support tumor growth and survival [3–5].