Highlights
- •Targeted sequencing was performed on matched primary localized and metastatic SCCs.
- •ERBB4 and STK11 mutations co-occurred in primary localized SCC.
- •Mutations in the Wnt pathway were detected in metastatic SCC only.
Abstract
Background
Cutaneous squamous cell carcinoma (SCC) is the second most common type of skin cancer
and is responsible for over one million cases annually. While only 3–5 % of SCCs metastasize,
those that do are associated with significant morbidity and mortality. Using gene
mutations to help predict metastasis and select therapeutics is still being explored.
Objective
To present novel data from targeted sequencing of 20 case-matched localized and metastatic
high-risk SCCs.
Methods
A cancer-associated gene panel of 76 genes was run from formalin-fixed paraffin-embedded
samples of 20 case-matched localized (10) and metastatic (10) high-risk SCCs (Vela
Diagnostics).
Results
Using spatial clustering analysis, primary driver mutations were identified asEGFR in localized SCC and CDH1 in metastatic SCC. ERBB4 and STK11 were found to be significant co-occurring mutations in localized SCC. Pathway analyses
showed the RTK/RAS, TP53, TGF-b, NOTCH1, PI3K, and cell cycle pathways to be highly relevant in all high-risk SCCs with the Wnt
pathway enhanced in metastatic SCC only.
Conclusions
This study compared gene mutations between localized and metastatic SCC with the intent
of identifying key differences and new potential targeted treatment options. To our
knowledge, the co-occurrence ofERBB4 and STK11 mutations has not been previously reported. Targeted inhibition of CDH1 and the Wnt pathway should be further explored in metastatic SCC.
Keywords
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Article info
Publication history
Published online: May 29, 2020
Accepted:
May 12,
2020
Received in revised form:
May 1,
2020
Received:
January 15,
2020
Identification
Copyright
Published by Elsevier B.V. on behalf of Japanese Society for Investigative Dermatology.
