mTOR signaling is hyperactive in sporadic sacral chordomas: in one study 10 out of 10 sacral chordomas exhibited phosphorylation of Ribosomal protein s6 and EIF4EBP1 by immunohistochemistry[4] Partial or complete PTEN (gene) deficiency is observed in nearly all sacral chordomas[4] In a study of 49 chordomas Akt, TSC2, and EIF4EBP1 were phosphorylated in 92%, 96% and 98% of cases, respectively.[5] In a tissue microarray containing 21 chordomas Platelet-derived growth factor receptor-beta (PDGFR-b), epidermal growth factor receptor (EGFR), KIT (CD117) and HER2 were detected in 100%, 67%, 33% and 0% of cases, respectively.[6] The CDKN2A (p16) and CDKN2B (p15) loci on chromosome 9p21 are frequently deleted in chordomas[7] Another study found CDKN2A immunoreactivity in just 4% of cases.[5] 62% of chordomas express the High Molecular Weight Melanoma Associated Antigen, also known as Chondroitin sulfate proteoglycan 4 (CSPG4) which has been the target of immune therapy.[8] In 2009, scientists discovered that an inherited gene duplication is responsible for the familial form of this disorder.[9] Familial chordoma are rare, with an estimated rate of 0.4% in all Chordomas.[10]