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Comparative Genomic Profiling of Refractory and Metastatic Penile and Nonpenile Cutaneous Squamous Cell Carcinoma:

Joseph M Jacob1, Elizabeth K Ferry, Laurie M Gay2

  • 1Upstate Medical University , Syracuse , New York.

The Journal of Urology
|October 7, 2018
PubMed
Abstract

Insights

Metastatic penile squamous cell carcinoma has unique genomic features. While not ideal for immunotherapy, over 25% of cases may benefit from targeted therapies for MTOR, DNA repair, and tyrosine kinase pathways.

Area of Science:

  • Oncology
  • Genomics
  • Cancer Research

Background:

  • Metastatic penile squamous cell carcinoma (mPSCC) is an aggressive cancer with limited therapeutic options.
  • Understanding its genomic landscape is crucial for developing targeted treatments.

Purpose of the Study:

  • To compare the genomic alterations in mPSCC with nonpenile metastatic cutaneous squamous cell carcinoma (mCSCC).
  • To identify potential targeted therapy opportunities in mPSCC.

Main Methods:

  • Comprehensive genomic profiling using next-generation sequencing on DNA from 78 mPSCC and 338 mCSCC samples.
  • Analysis of tumor mutational burden (TMB) and microsatellite instability (MSI).

Main Results:

  • mPSCC showed potential targeted therapy opportunities in MTOR (NF1, PTEN), DNA repair (BRCA2, ATM), and tyrosine kinase (EGFR, FGFR3, ERBB2) pathways.
  • mCSCC had significantly higher TMB than mPSCC, suggesting greater potential responsiveness to immunotherapy.
  • Microsatellite high status and CD274 (PD-L1) amplification were rare in both types.

Conclusions:

  • mPSCC possesses distinct genomic features compared to nonpenile mCSCC.
  • Despite low TMB and MSI, mPSCC may benefit from therapies targeting MTOR, DNA repair, and tyrosine kinase pathways.
Keywords:
DMA mutational analysiscarcinomagenomicsneoplasm metastasispenile neoplasmssquamous cell

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