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Integrative multi-region molecular profiling of primary prostate cancer in men with synchronous lymph node metastasis

Author

Listed:
  • Udit Singhal

    (Michigan Medicine
    Mayo Clinic
    Michigan Medicine
    Michigan Medicine)

  • Srinivas Nallandhighal

    (Michigan Medicine)

  • Jeffrey J. Tosoian

    (Vanderbilt University
    Vanderbilt-Ingram Cancer Center)

  • Kevin Hu

    (Michigan Medicine)

  • Trinh M. Pham

    (Michigan Medicine)

  • Judith Stangl-Kremser

    (Michigan Medicine
    Medical University of Vienna)

  • Chia-Jen Liu

    (University of Michigan)

  • Razeen Karim

    (University of Michigan)

  • Komal R. Plouffe

    (Michigan Medicine
    Michigan Medicine)

  • Todd M. Morgan

    (Michigan Medicine
    Michigan Medicine)

  • Marcin Cieslik

    (Michigan Medicine
    Michigan Medicine
    Michigan Medicine)

  • Roberta Lucianò

    (Universita Vita-Salute San Raffaele)

  • Shahrokh F. Shariat

    (Medical University of Vienna)

  • Nadia Finocchio

    (Universita Vita-Salute San Raffaele)

  • Lucia Dambrosio

    (Universita Vita-Salute San Raffaele)

  • Claudio Doglioni

    (Universita Vita-Salute San Raffaele)

  • Arul M. Chinnaiyan

    (Michigan Medicine
    Michigan Medicine
    Michigan Medicine
    Michigan Medicine)

  • Scott A. Tomlins

    (Michigan Medicine)

  • Alberto Briganti

    (Universita Vita-Salute San Raffaele)

  • Ganesh S. Palapattu

    (Michigan Medicine
    Michigan Medicine
    Medical University of Vienna)

  • Aaron M. Udager

    (Michigan Medicine
    Michigan Medicine
    Michigan Medicine)

  • Simpa S. Salami

    (Michigan Medicine
    Michigan Medicine
    Michigan Medicine)

Abstract

Localized prostate cancer is frequently composed of multiple spatially distinct tumors with significant inter- and intra-tumoral molecular heterogeneity. This genomic diversity gives rise to many competing clones that may drive the biological trajectory of the disease. Previous large-scale sequencing efforts have focused on the evolutionary process in metastatic prostate cancer, revealing a potential clonal progression to castration resistance. However, the clonal origin of synchronous lymph node (LN) metastases in primary disease is still unknown. Here, we perform multi-region, targeted next generation sequencing and construct phylogenetic trees in men with prostate cancer with synchronous LN metastasis to better define the pathologic and molecular features of primary disease most likely to spread to the LNs. Collectively, we demonstrate that a combination of histopathologic and molecular factors, including tumor grade, presence of extra-prostatic extension, cellular morphology, and oncogenic genomic alterations are associated with synchronous LN metastasis.

Suggested Citation

  • Udit Singhal & Srinivas Nallandhighal & Jeffrey J. Tosoian & Kevin Hu & Trinh M. Pham & Judith Stangl-Kremser & Chia-Jen Liu & Razeen Karim & Komal R. Plouffe & Todd M. Morgan & Marcin Cieslik & Rober, 2024. "Integrative multi-region molecular profiling of primary prostate cancer in men with synchronous lymph node metastasis," Nature Communications, Nature, vol. 15(1), pages 1-9, December.
  • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-48629-y
    DOI: 10.1038/s41467-024-48629-y
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