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Deletion of 3p13-14 locus spanning FOXP1 to SHQ1 cooperates with PTEN loss in prostate oncogenesis

Author

Listed:
  • Haley Hieronymus

    (Memorial Sloan Kettering Cancer Center)

  • Phillip J. Iaquinta

    (Memorial Sloan Kettering Cancer Center)

  • John Wongvipat

    (Memorial Sloan Kettering Cancer Center)

  • Anuradha Gopalan

    (Memorial Sloan Kettering Cancer Center)

  • Rajmohan Murali

    (Memorial Sloan Kettering Cancer Center)

  • Ninghui Mao

    (Memorial Sloan Kettering Cancer Center)

  • Brett S. Carver

    (Memorial Sloan Kettering Cancer Center
    Memorial Sloan Kettering Cancer Center)

  • Charles L. Sawyers

    (Howard Hughes Medical Institute)

Abstract

A multigenic locus at 3p13-14, spanning FOXP1 to SHQ1, is commonly deleted in prostate cancer and lost broadly in a range of cancers but has unknown significance to oncogenesis or prognosis. Here, we report that FOXP1-SHQ1 deletion cooperates with PTEN loss to accelerate prostate oncogenesis and that loss of component genes correlates with prostate, breast, and head and neck cancer recurrence. We demonstrate that Foxp1-Shq1 deletion accelerates prostate tumorigenesis in mice in combination with Pten loss, consistent with the association of FOXP1-SHQ1 and PTEN loss observed in human cancers. Tumors with combined Foxp1-Shq1 and Pten deletion show increased proliferation and anaplastic dedifferentiation, as well as mTORC1 hyperactivation with reduced Akt phosphorylation. Foxp1-Shq1 deletion restores expression of AR target genes repressed in tumors with Pten loss, circumventing PI3K-mediated repression of the androgen axis. Moreover, FOXP1-SHQ1 deletion has prognostic relevance, with cancer recurrence associated with combined loss of PTEN and FOXP1-SHQ1 genes.

Suggested Citation

  • Haley Hieronymus & Phillip J. Iaquinta & John Wongvipat & Anuradha Gopalan & Rajmohan Murali & Ninghui Mao & Brett S. Carver & Charles L. Sawyers, 2017. "Deletion of 3p13-14 locus spanning FOXP1 to SHQ1 cooperates with PTEN loss in prostate oncogenesis," Nature Communications, Nature, vol. 8(1), pages 1-10, December.
    • Handle: RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_s41467-017-01198-9
    DOI: 10.1038/s41467-017-01198-9
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    Cited by:

    1. Ning Zhang & Luuk Harbers & Michele Simonetti & Constantin Diekmann & Quentin Verron & Enrico Berrino & Sara E. Bellomo & Gabriel M. C. Longo & Michael Ratz & Niklas Schultz & Firas Tarish & Peng Su &, 2024. "High clonal diversity and spatial genetic admixture in early prostate cancer and surrounding normal tissue," Nature Communications, Nature, vol. 15(1), pages 1-17, December.

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