Genomic Insights into Cutaneous Squamous Cell Carcinoma.

Area of Science:

• Oncology
• Genomics
• Molecular Biology

Background:

• Cutaneous squamous cell carcinoma (cSCC) is a common skin cancer with a poorly understood genomic landscape.
• Characterizing cSCC's molecular drivers is crucial for identifying therapeutic targets.
• Existing research has not comprehensively mapped the genomic alterations in cSCC.

Purpose of the Study:

• To comprehensively characterize the genomic landscape of cSCC.
• To identify key molecular drivers and potential therapeutic targets in cSCC.
• To utilize data from the American Association for Cancer Research (AACR) Project Genomics, Evidence, Neoplasia, Information, Exchange (GENIE) consortium.

Main Methods:

• Retrospective cohort analysis of cSCC samples from the AACR Project GENIE database.
• Utilized cBioPortal for data access and analysis.
• Identified recurrent somatic and copy-number alterations, performed gene-gene co-occurrence testing, and conducted subgroup analyses by sex and race.

Main Results:

• Recurrent mutations identified in TP53 (83.5%), NOTCH1 (56.3%), KMT2D (47.0%), CDKN2A (44.4%), and TERT (41.4%).
• Detected alterations disrupt key pathways including p53, cell-cycle control, Notch signaling, and epigenetic regulation.
• Observed statistically significant gene-gene co-occurrence patterns and evaluated mutation frequency differences across demographic subgroups.

Conclusions:

• This large-scale genomic analysis defines recurrent alterations in cSCC, revealing integrated pathway disruptions.
• Findings enhance understanding of cSCC's molecular architecture, impacting genomic integrity, differentiation, and proliferation.
• Provides a foundation for future research into targeted diagnostic and therapeutic strategies for cSCC.