Our findings of PTENP1 (PBCS), TNS1 (EPIC), and SYNJ2 (CGEM) are consistent with known breast cancer mutations in PI3K/PTEN [107, 108] and SYNJ2. That both PI(3,4,5)P3 and PI(3,4)P2 are required to achieve and sustain a malignancy, has been formulated as the “two PI hypothesis”[109] Except for the known PRCKQ, which is regulated by phospholipids via the PI(4,5)P2–PLC–DAG route, however, our analysis identified few genes along the AKT/TSC/mTOR pathway, which is controlled by the “two PIs”. The gene discussed is HSPG2; the disease is breast cancer.