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Analysis of mutations in cutaneous squamous cell carcinoma reveals novel genes and mutations associated with patient-specific characteristics and metastasis: a systematic review

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Abstract

Cutaneous squamous cell carcinoma (SCC) causes approximately 1,000,000 cases and 9000 deaths each year in the United States. While individual tumor sequencing studies have discovered driver mutations in SCC, there has yet to be a review and subsequent analysis synthesizing current studies. To conduct a comprehensive synthesis and analysis of SCC sequencing studies with individual patient-level data, a comprehensive literature search was performed. Statistical analyses were performed to identify trends. Studies meeting inclusion criteria included a total of 279 patients (189 localized SCCs, 90 metastatic SCCs). Several mutations were correlated with demographic characteristics (TP53, MLL4, BRCA2, COL4A1). TP53, TERT, SPEN, MLL3, and NOTCH2 mutations were significantly more likely to be found in metastatic versus localized SCCs even after the Bonferroni correction for multiple comparisons. Silent mutations were found more in localized SCCs than metastatic SCCs, and nonsense mutations were found more in metastatic SCCs than localized SCCs (p = 0.0003 and p = 0.04, respectively). Additional mutations were identified that have not yet been explored in SCC including AHNAK2, LRP1B, TRIO, MDN1, COL4A2, SVIL, VPS13C, DST, DMD, and DYSF. Overall, novel mutations were identified and differences between mutation patterns in localized and metastatic SCCs were found. These findings may have clinical applications.

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Data availability

All data used is publicly available. Summary data is available upon request to authors and can be deposited to an online portal.

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Author information

Authors and Affiliations

  1. Department of Dermatology, University of Nebraska Medical Center, Omaha, NE, 68198, USA

    Marissa B. Lobl, Dillon Clarey & Ashley Wysong

  2. Leon S. McGoogan Health Sciences Library, University of Nebraska Medical Center, Omaha, NE, USA

    Cynthia Schmidt

  3. Department of Biostatistics, University of Nebraska Medical Center, Omaha, NE, USA

    Christopher Wichman

Authors
  1. Marissa B. Lobl
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  2. Dillon Clarey
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  3. Cynthia Schmidt
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  4. Christopher Wichman
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  5. Ashley Wysong
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Contributions

ML performed conceptualization, investigation, data curation, formal analysis, visualization, and writing of the original draft. DC performed reviewing and editing of writing. CS performed data curation, methodology, and editing of writing. CW performed formal analysis and editing of writing. AW performed conceptualization, supervision, methodology, resources, and reviewing and editing of writing.

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Correspondence to Ashley Wysong.

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Dr. Wysong serves as a Research Principal Investigator for Castle Biosciences.

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Supplementary Information

Below is the link to the electronic supplementary material.

403_2021_2213_MOESM1_ESM.docx

Supplementary file1 Supplementary Figure 1: Distribution and subtypes of mutations by protein domain for mutations measured in all studies (DOCX 103 KB)

Supplementary file2 Supplementary Table 1: Cohort characteristics (DOCX 20 KB)

Supplementary file3 Supplementary Table 2: Inclusion and exclusion criteria (DOCX 31 KB)

403_2021_2213_MOESM4_ESM.docx

Supplementary file4 Supplementary Table 3: Pattern counts for co-occurring mutations in metastatic SCC for genes measured in all studies (DOCX 28 KB)

Supplementary file5 Supplementary Table 4: Mutation subtypes by group (DOCX 21 KB)

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Lobl, M.B., Clarey, D., Schmidt, C. et al. Analysis of mutations in cutaneous squamous cell carcinoma reveals novel genes and mutations associated with patient-specific characteristics and metastasis: a systematic review. Arch Dermatol Res 314, 711–718 (2022). https://doi.org/10.1007/s00403-021-02213-2

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