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Molecular Landscape of Skin Carcinomas

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New Therapies in Advanced Cutaneous Malignancies

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Abstract

Non-melanoma skin cancers are considered to have one of the highest rates of mutations amongst all human tumours. The majority of aberrations are caused by UV exposure, which induces characteristic “UV signature” mutations. Basal cell carcinoma (BCC) is the most prevalent malignancy amongst the Caucasian population. The primary hallmark of BCCs are aberrations in the Hedgehog (HH) pathway. The PTCH1 gene, a suppressing component of HH signalling, is altered in up to 75% of BCC cases. Nevertheless, several protooncogenes and suppressor genes, including SMO, TP53, MYCN, NOTCH1/2, as well as Hippo pathway proteins, are also significantly deregulated in skin cancers. Other aberrations, reported in skin cancers, affect the TERT promoter, detoxifying proteins, and the NFκB pathway signalling. Moreover, alterations of the TP53 gene are the most frequent mutations in squamous cell carcinomas (SCCs). Genes involved in cell cycle control (CDKN2A, MYC), signalling (EGFR, FGFR1) and differentiation (TP63, SOX2) are often altered in SCCs. In Merkel cell carcinomas (MCCs) mutations occur in RB1, TP53, NOTCH1/2 and in the PI3K-AKT pathway genes. Aberrations in MCCs result from UV exposure as well as Merkel cell polyomavirus infection. It is worth noting that sebaceous carcinoma has a similar spectrum of mutations as SCCs.

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Acknowledgements

The authors thank Prof. Ewa Bartnik for proofreading of the text.

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Authors and Affiliations

  1. Department of Soft Tissue/Bone, Sarcoma and Melanoma, Maria Sklodowska-Curie National Research Institute of Oncology, Warsaw, Poland

    Anna M. Czarnecka & Karolina Stachyra

  2. Department of Experimental Pharmacology, Mossakowski Medical Research Institute, Polish Academy of Sciences, Warsaw, Poland

    Anna M. Czarnecka

  3. Faculty of Medicine, Medical University of Warsaw, Warsaw, Poland

    Karolina Stachyra

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  1. Anna M. Czarnecka
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Correspondence to Anna M. Czarnecka .

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  1. Department of Soft Tissue/Bone Sarcoma and Melanoma, Maria Sklodowska-Curie National Research Institute of Oncology, Warsaw, Poland

    Piotr Rutkowski

  2. Department of Medicine and Surgery, Unit of Medical OncologyUniversity of Perugia, Perugia, Italy

    Mario Mandalà

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Czarnecka, A.M., Stachyra, K. (2021). Molecular Landscape of Skin Carcinomas. In: Rutkowski, P., Mandalà, M. (eds) New Therapies in Advanced Cutaneous Malignancies. Springer, Cham. https://doi.org/10.1007/978-3-030-64009-5_3

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