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The gene encoding the main signaling molecules of the Wnt signaling pathways (the Wnt proteins) was discovered almost four decades ago by Nüsslein-Volhard and Wieschaus. They identified and originally named the gene "wingless" (wg) after a phenotype discovered during their landmark genetic screen in Drosophila for body pattern defects. At around the same time, another researcher named Harold Varmus found that a murine tumor virus activates the mammalian wg homolog, Int-1, which...
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WNT Pathway Mutations in Metachronous Oligometastatic Castration-Sensitive Prostate Cancer.

Philip Sutera1, Matthew P Deek2, Kim Van der Eecken3

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|January 28, 2023
PubMed
Summary
This summary is machine-generated.

Genomic alterations in WNT signaling occur in 11.2% of men with oligometastatic castration-sensitive prostate cancer (omCSPC) and are linked to visceral metastases. Despite a poorer prognosis, these patients may still benefit from metastasis-directed therapy (MDT).

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Area of Science:

  • Oncology
  • Genetics
  • Molecular Biology

Background:

  • WNT signaling pathway is crucial in prostate cancer development and progression.
  • Oligometastatic castration-sensitive prostate cancer (omCSPC) is a distinct disease state where metastasis-directed therapy (MDT) improves progression-free survival.

Purpose of the Study:

  • To investigate the clinical implications of WNT signaling pathway genomic alterations in men with omCSPC.
  • To correlate WNT pathway mutations with clinical factors and survival outcomes in omCSPC patients.

Main Methods:

  • International multi-institutional retrospective study of 277 omCSPC patients.
  • Targeted DNA sequencing for WNT pathway mutations (APC, RNF43, CTNNB1).
  • Statistical analysis including Pearson χ², Mann-Whitney U tests, and multivariable Cox regression; Kaplan-Meier survival analysis.

Main Results:

  • Pathogenic WNT pathway mutations found in 11.2% of patients.
  • WNT mutations associated with higher rates of visceral metastases (22.6% vs 2.8%) and lower rates of lymph node metastases (29.0% vs 50.4%).
  • WNT pathway mutations significantly correlated with worse overall survival (HR, 3.87).

Conclusions:

  • Somatic WNT pathway alterations are present in about 11% of omCSPC patients, associated with increased visceral metastases.
  • Patients with WNT alterations have a worse natural disease history.
  • Metastasis-directed therapy (MDT) may offer benefits to omCSPC patients with WNT pathway alterations.