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Distinct mutational landscape of inverted urothelial papilloma

Mahmut Akgul1, Gregory T MacLennan2, Liang Cheng3

  • 1Department of Pathology, University of Texas MD Anderson Cancer Center, Houston, TX, USA.

The Journal of Pathology
|May 24, 2019
PubMed

Insights

Inverted urothelial papillomas (IUPs) show HRAS gene mutations within the MAPK/ERK pathway. These benign tumors do not recur or progress, distinguishing them molecularly from urothelial carcinoma.

Area of Science:

  • Uro-oncology
  • Molecular pathology
  • Genetics

Background:

  • Inverted urothelial papillomas (IUPs) are rare bladder tumors.
  • Distinguishing IUPs from urothelial carcinoma is critical for patient management.
  • Previous studies suggested distinct molecular profiles for IUPs.

Purpose of the Study:

  • To investigate the genetic landscape of inverted urothelial papillomas.
  • To identify specific gene mutations associated with IUP development.
  • To compare the molecular characteristics of IUPs with urothelial carcinoma.

Main Methods:

  • Somatic mutation profiling of IUPs.
  • Targeted sequencing of key oncogenes and tumor suppressors.
  • Analysis of mutations in MAPK/ERK pathway, TERT promoter, FGFR3, and TP53/RB1 genes.

Main Results:

  • All analyzed IUPs exhibited mutations in the MAPK/ERK pathway, specifically within the HRAS gene.
  • No mutations were detected in TERT promoter, FGFR3, or TP53/RB1 genes in IUPs.
  • No instances of recurrence or progression were observed in patients with IUPs.

Conclusions:

  • IUPs are benign tumors that do not recur or progress.
  • IUPs possess a distinct molecular signature, characterized by HRAS mutations, differentiating them from urothelial carcinoma.
  • The findings support unique molecular pathways for IUP development compared to urothelial carcinoma.
Keywords:
FGFR3MAPK/ERK pathwayTERT promoter mutationinverted urothelial papillomamolecular geneticsurinary bladder

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