Journal of Clinical and Investigative Dermatology

Research Article

Sequencing of within-Subject Primary and Metastatic Cutaneous Squamous Cell Carcinomas Reveals Novel Diagnostic and Therapeutic Targets for Metastatic Disease

Maggie Chow1, Sarah Murray2, Adam Miller3, Rachel Chang3, Brian Hinds3, Bryan Sun3, Shang I Brian Jiang3*

1Department of Dermatology, Keck Medical Center of the University of Southern California, USA
2Department of Pathology, University of California, San Diego, USA
3Department of Dermatology University of California, San Diego, USA
*Address for Correspondence: Shang I. Brian Jiang, Department of Dermatology, University of California, San Diego, Mohs Surgery and Dermatologic Oncology Fellowship 8899 University Center Lane Ste 350 San Diego CA 92122, USA Email: S2jiang@ucsd.edu
Submission: 03 November, 2022
Accepted: 05 December, 2022
Published: 09 December, 2022
Copyright: © 2022 Chow M, et al. This is an open access article distributed under the Creative Commons Attri-bution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Cutaneous squamous cell carcinoma (cSCC) is a common type of skin cancer that rarely metastasizes. However, metastasis is associated with significant morbidity and mortality. Thus, additional study on the molecular markers that prognosticate aggressive behavior of cSCC are needed to improve diagnostic and therapeutic tools. Our goal was to identify genetic mutations in cSCCs that may be markers of or contribute to metastatic risk. A matched case-control study of high depth sequencing of 397 genes in matched metastatic and primary cSCC from 12 patients was performed in 2020. A follow up of at least 5 years was required for all patients. Identified mutations were compared between the two groups. Over 1,000 deleterious mutations were identified in metastatic and primary cSCC samples, of which TP53, LRP1B and FAT1 mutations were most common overall. In comparing between the metastatic and primary cSCCs, 53 genes were unique to the metastatic group. Mutations in SETBP1, AR, and TSHR were most common and unique to the metastatic samples. Though also found in primary cSCC, NOTCH1 was significantly more commonly mutated in metastatic samples than primary cSCC.We nominate several genes that, when mutated, serve as markers for more aggressive behavior in cSCCs. Further investigations into this complex but important topic are needed.