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Comprehensive characterization of PTEN mutational profile in a series of 34,129 colorectal cancers

Author

Listed:
  • Ilya G. Serebriiskii

    (Program in Molecular Therapeutics, Fox Chase Cancer Center
    Kazan Federal University, Russian Federation)

  • Valery Pavlov

    (Kazan Federal University, Russian Federation
    Moscow Institute of Physics and Technology, Russian Federation)

  • Rossella Tricarico

    (Program in Molecular Therapeutics, Fox Chase Cancer Center
    University of Pavia)

  • Grigorii Andrianov

    (Program in Molecular Therapeutics, Fox Chase Cancer Center
    Kazan Federal University, Russian Federation)

  • Emmanuelle Nicolas

    (Program in Molecular Therapeutics, Fox Chase Cancer Center)

  • Mitchell I. Parker

    (Program in Molecular Therapeutics, Fox Chase Cancer Center
    Drexel University College of Medicine)

  • Justin Newberg

    (Foundation Medicine Inc)

  • Garrett Frampton

    (Foundation Medicine Inc)

  • Joshua E. Meyer

    (Program in Molecular Therapeutics, Fox Chase Cancer Center
    Fox Chase Cancer Center)

  • Erica A. Golemis

    (Program in Molecular Therapeutics, Fox Chase Cancer Center
    Lewis Katz School of Medicine at Temple University)

Abstract

Loss of expression or activity of the tumor suppressor PTEN acts similarly to an activating mutation in the oncogene PIK3CA in elevating intracellular levels of phosphatidylinositol (3,4,5)-trisphosphate (PIP3), inducing signaling by AKT and other pro-tumorigenic signaling proteins. Here, we analyze sequence data for 34,129 colorectal cancer (CRC) patients, capturing 3,434 PTEN mutations. We identify specific patterns of PTEN mutation associated with microsatellite stability/instability (MSS/MSI), tumor mutational burden (TMB), patient age, and tumor location. Within groups separated by MSS/MSI status, this identifies distinct profiles of nucleotide hotspots, and suggests differing profiles of protein-damaging effects of mutations. Moreover, discrete categories of PTEN mutations display non-identical patterns of co-occurrence with mutations in other genes important in CRC pathogenesis, including KRAS, APC, TP53, and PIK3CA. These data provide context for clinical targeting of proteins upstream and downstream of PTEN in distinct CRC cohorts.

Suggested Citation

  • Ilya G. Serebriiskii & Valery Pavlov & Rossella Tricarico & Grigorii Andrianov & Emmanuelle Nicolas & Mitchell I. Parker & Justin Newberg & Garrett Frampton & Joshua E. Meyer & Erica A. Golemis, 2022. "Comprehensive characterization of PTEN mutational profile in a series of 34,129 colorectal cancers," Nature Communications, Nature, vol. 13(1), pages 1-17, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-29227-2
    DOI: 10.1038/s41467-022-29227-2
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