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Updated: Apr 18, 2026
Comparative Lesions Analysis Through a Targeted Sequencing Approach
Published on: November 5, 2019
Genomic analysis of metastatic cutaneous squamous cell carcinoma
Yvonne Y Li1, Glenn J Hanna2, Alvaro C Laga3
1Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts. Broad Institute, Cambridge, Massachusetts.
Purpose:
A rare 5% of cutaneous squamous cell carcinomas (cSCC) metastasize, lack FDA-approved therapies, and carry a poor prognosis. Our aim was to identify recurrent genomic alterations in this little-studied population of metastatic cSCCs.
Experimental Design:
We performed targeted sequencing of 504 cancer-associated genes on lymph node metastases in 29 patients with cSCC and identified mutations and somatic copy-number alterations associated with metastatic cSCC. We determined significantly mutated, deleted, and amplified genes and associated genomic alterations with clinical variables.
Results:
The cSCC genome is heterogeneous with widely varying numbers of genomic alterations and does not appear to be associated with human papillomavirus. We found previously identified recurrently altered genes (TP53, CDKN2A, NOTCH1/2) but also a wide spectrum of oncogenic mutations affecting RAS/RTK/PI3K, squamous differentiation, cell cycle, and chromatin remodeling pathway genes. Specific mutations in known oncogenic drivers and pathways were correlated with inferior patient outcomes. Our results suggest potential therapeutic targets in metastatic cSCC, including PIK3CA, FGFR3, BRAF, and EGFR, similar to those reported in SCCs of the lung and head and neck, suggesting that clinical trials could be developed to accrue patients with SCCs from multiple sites of origin.
Conclusions:
We have genomically characterized a rare cohort of 29 metastatic cSCCs and identified a diverse array of oncogenic alterations that can guide future studies of this disease.
Insights
Genomic analysis of metastatic cutaneous squamous cell carcinomas (cSCC) reveals diverse oncogenic alterations. These findings identify potential therapeutic targets for this rare and aggressive cancer, guiding future treatment strategies.
Area of Science:
- Genomics
- Oncology
- Cancer Biology
Background:
- Metastatic cutaneous squamous cell carcinoma (cSCC) is rare (5%), lacks targeted therapies, and has a poor prognosis.
- Understanding the genomic landscape of metastatic cSCC is crucial for developing effective treatments.
Purpose of the Study:
- To identify recurrent genomic alterations in metastatic cSCC.
- To correlate genomic alterations with clinical outcomes.
- To discover potential therapeutic targets for metastatic cSCC.
Main Methods:
- Targeted sequencing of 504 cancer-associated genes in lymph node metastases from 29 cSCC patients.
- Identification of mutations and somatic copy-number alterations.
- Correlation of genomic alterations with clinical variables.
Main Results:
- Metastatic cSCC exhibits genomic heterogeneity, unrelated to human papillomavirus.
- Recurrently altered genes (TP53, CDKN2A, NOTCH1/2) and novel oncogenic mutations in key pathways were identified.
- Mutations in PIK3CA, FGFR3, BRAF, and EGFR pathways are potential therapeutic targets, similar to other SCCs.
Conclusions:
- Genomic characterization of metastatic cSCC reveals a diverse set of oncogenic alterations.
- Identified alterations provide a foundation for future research and therapeutic development in metastatic cSCC.
