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Table 1 Phosphatidylinositol 3-kinase pathway alterations in human breast cancers by molecular subtype

From: Mutations in the phosphatidylinositol 3-kinase pathway: role in tumor progression and therapeutic implications in breast cancer

    Frequency  
Gene (protein) Alteration Effect on signaling Luminal (ER+) HER2+ Basal (TN) Reference
ErbB2 (HER2) Amplification or overexpression Hyperactivation of ErbB2 signaling (PI3K, MEK) 10% ~100% 0% [3032]
PTEN Loss-of-function mutation or reduced expression Hyperactivation of PI3K signaling 29-44% 22% 67% [6, 8, 104, 105]
PIK3CA (p110α/PI3K) Activating mutation Hyperactivation of PI3K signaling 28-47% 23-33% 8-25% [6, 52, 6668, 105107]
PIK3CB (p110β/PI3K) Amplification Unknown   5% of all cases   [62]
IGF1R and INSR (IGF-1R, InsR) Receptor activation, IGF1R amplification Activates IGF-IR/InsR signaling (PI3K, MEK) 41-48% 18-64% 42% [108, 109]
FGFR1 Amplification, activating mutation Hyperactivation of FGFR signaling (PI3K, MEK) 8.6-11.6% 5.4% 5.6% [63, 110]
RPS6K1 (p70S6K) Amplification Unknown   3.8-12.5% of all cases   [111]
INPP4B Reduced expression or genomic loss Hyperactivation of PI3K signaling 10-33% 54% 53% [64, 112]
PIK3R1 (p85α/PI3K) Inactivating mutation Derepression of catalytic activity of p110α   2% of all cases   [113]
AKT1 Activating mutation Hyperactivation of AKT 2.6-3.8% 0% 0% [65, 66, 106, 114]
AKT2 Amplification Hyperactivation of AKT   2.8% of all cases   [115]
EGFR Amplification Hyperactivation of EGFR signaling (PI3K, MEK)   0.8% of all cases   [116]
PDK1 Amplification or overexpression Hyperactivation of PDK1 (AKT, TORC1) 22% 22% 38% [117]
KRAS Activating mutation Hyperactivation of PI3K and MEK   4-6% of all cases   [118, 119]
  1. EGFR, epidermal growth factor receptor; ER, estrogen receptor; FGFR, fibroblast growth factor receptor; HER, human epidermal growth factor receptor; IGF-1R, insulin-like growth factor-1 receptor; INPP4B, inositol polyphosphate-4-phosphatase, type II; InsR, insulin receptor; MEK, mitogen-activated protein kinase kinase; PDK1, phosphoinositide-dependent kinase 1; PI3K, phosphatidylinositol 3-kinase; TN, triple negative.