Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2024 May 22;16(11):1956.
doi: 10.3390/cancers16111956.

Mutational Profiles of Cutaneous Squamous Cell Carcinomas with Different Patterns of Clinical Aggression from Head and Neck Regions

Maria Colombino  1 , Giuseppe Palmieri  2 , Manuela Rodio  3   4 , Matilde Tettamanzi  3   4 , Silvia Rampazzo  3   4 , Raffaello Margani  3   5 , Emilio Trignano  3   5 , Antonio Cossu  6 , Maria Antonietta Fedeli  6 , Giovanni Maria Fadda  7 , Corrado Rubino  3   5
Affiliations

Mutational Profiles of Cutaneous Squamous Cell Carcinomas with Different Patterns of Clinical Aggression from Head and Neck Regions

Maria Colombino et al. Cancers (Basel). .

Abstract

Cutaneous squamous cell carcinoma is a prevalent malignancy with a rising incidence and a notably high mutational load. Exploring the genetic nuances of cSCC and investigating molecular approaches stands as a potential avenue for improving outcomes in high-risk patients. This retrospective case-control study involved two cohorts, one of 14 patients (the "discovery cohort") and the other of 12 patients (the "validation cohort"), with cSCC located in the head/neck anatomical region and diagnosed at the pT2 stage. Overall, cases developed early local relapses of the disease, whereas controls never relapsed during the entire follow-up period. A next-generation sequencing (NGS) approach conducted on histological samples revealed that TP53 and CDKN2A were the most frequently mutated genes in our series. No specific mutations were identified as potential prognostic or therapeutic targets. Controls exhibited a tendency toward a higher mutational rate compared to cases. It is possible that an increased number of mutations could prompt the cSCC to expose more antigens, becoming more immunogenic and facilitating recognition by the immune system. This could enhance and sustain the immunological response, potentially preventing future recurrences.

Keywords: cutaneous squamous cell carcinoma (cSCC); immunogenicity; mutation profile; next-generation sequencing (NGS); non-melanoma skin cancer; recurrent cSCC.

PubMed Disclaimer

Conflict of interest statement

The authors declare no conflicts of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript; or in the decision to publish the results.

Figures

Figure 1
Figure 1
Spectrum and distribution of pathogenic/likely pathogenic mutations (dark blue squares) among cases (C) and controls (CTRL) from the discovery cohort. In light blue, the VUS variants of the KDR and KIT genes are indicated. Numbers in squares indicate the total number of multiple mutations detected in each sample.
Figure 2
Figure 2
Distribution and frequencies of mutated genes in cases and controls by oncogenic pathways. Receptor Tyrosine Kinase (RTK)/RAS pathway: FGFR1, ERBB2, and FLT3; PI3K/PTEN pathway: PIK3CA, PTEN, and STK11; P53-ATM pathway: TP53 and ATM; cell cycle pathway: CDKN2A and RB1; NOTCH pathway: NOTCH1; other genes: SMAD4, IDH2, GNAS, EZH2, KIT, and KDR.
Figure 3
Figure 3
Spectrum and distribution of pathogenic/likely pathogenic mutations (dark blue squares) among cases (v-C) and controls (v-CTRL) from the validation cohort. In light blue are indicated the VUS variants of the KDR and KIT genes. Numbers in the squares indicate the total of multiple mutations detected in each sample.
See this image and copyright information in PMC

References

    1. Kallini J.R., Hamed N., Khachemoune A. Squamous cell carcinoma of the skin: Epidemiology, classification, management, and novel trends. Int. J. Dermatol. 2015;54:130–140. doi: 10.1111/ijd.12553. - DOI - PubMed
    1. Muzic J.G., Schmitt A.R., Wright A.C., Alniemi D.T., Zubair A.S., Olazagasti Lourido J.M., Sosa Seda I.M., Weaver A.L., Baum C.L. Incidence and Trends of Basal Cell Carcinoma and Cutaneous Squamous Cell Carcinoma: A Population-Based Study in Olmsted County, Minnesota, 2000 to 2010. Mayo Clin. Proc. 2017;92:890–898. doi: 10.1016/j.mayocp.2017.02.015. - DOI - PMC - PubMed
    1. Rubió-Casadevall J., Hernandez-Pujol A.M., Ferreira-Santos M.C., Morey-Esteve G., Vilardell L., Osca-Gelis G., Vilar-Coromina N., Marcos-Gragera R. Trends in incidence and survival analysis in non-melanoma skin cancer from 1994 to 2012 in Girona, Spain: A population-based study. Cancer Epidemiol. 2016;45:6–10. doi: 10.1016/j.canep.2016.09.001. - DOI - PubMed
    1. Rudolph C., Schnoor M., Eisemann N., Katalinic A. Incidence trends of nonmelanoma skin cancer in Germany from 1998 to 2010. J. Ger. Soc. Dermatol. 2015;13:788–798. doi: 10.1111/ddg.12690. - DOI - PubMed
    1. Xiang F., Lucas R., Hales S., Neale R. Incidence of nonmelanoma skin cancer in relation to ambient UV radiation in white populations, 1978-2012 empirical relationships. JAMA Dermatol. 2014;150:1063–1071. doi: 10.1001/jamadermatol.2014.762. - DOI - PubMed