Understanding the Molecular Genetics of Basal Cell Carcinoma
Open accessAbstract
Basal cell carcinoma (BCC) is the most common human cancer and represents a growing public health care problem. Several tumor suppressor genes and proto-oncogenes have been implicated in BCC pathogenesis, including the key components of the Hedgehog pathway, PTCH1 and SMO, the TP53 tumor suppressor, and members of the RAS proto-oncogene family. Aberrant activation of the Hedgehog pathway represents the molecular driver in basal cell carcinoma pathogenesis, with the majority of BCCs carrying somatic point mutations, mainly ultraviolet (UV)-induced, and/or copy-loss of heterozygosis in the PTCH1 gene. Recent advances in sequencing technology allowed genome-scale approaches to mutation discovery, identifying new genes and pathways potentially involved in BCC carcinogenesis. Mutational and functional analysis suggested PTPN14 and LATS1, both effectors of the Hippo–YAP pathway, and MYCN as new BCC-associated genes. In addition, emerging reports identified frequent non-coding mutations within the regulatory promoter sequences of the TERT and DPH3-OXNAD1 genes. Thus, it is clear that a more complex genetic network of cancer-associated genes than previously hypothesized is involved in BCC carcinogenesis, with a potential impact on the development of new molecular targeted therapies. This article reviews established knowledge and new hypotheses regarding the molecular genetics of BCC pathogenesis.
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Overexposure to sunlight is directly connected with the onset of skin cancers such as basal cell carcinoma (BSC), squamous cell carcinoma (SCC), and malignant melanoma (MM).
“Overexposure to sunlight is directly connected the with onset of skin cancers such as basal cell carcinoma (BSC) [165], squamous cell carcinoma (SCC) [166,167], and malignant melanoma (MM) [168,169].”
From Focus on UV-Induced DNA Damage and Repair—Disease Relevance and Protective Strategies (2020) · cites this paper as [165]
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- Authors
- Pellegrini, C., Maturo, M., Di Nardo, L., Ciciarelli, V., Gutiérrez García-Rodrigo, C., & Fargnoli, M.
- Affiliations
- University of L'Aquila (IT)
- Department of Dermatology, Department of Biotechnological and Applied Clinical Sciences, University of L’Aquila, 67100 L’Aquila, Italy
- Corresponding author
- Fargnoli, Maria
- Venue
- International Journal of Molecular Sciences
- Publisher
- MDPI AG
- Published
- 2017-11-22
- Volume
- 18
- Issue
- 11
- Pages
- 2485
- ISSN
- 1422-0067 (ISSN-L)
- PMC
- PMC5713451
- OpenAlex
- W2770311193
- Cited by
- 242
- References
- 123
- Citations by year
- 2026: 15 · 2025: 22 · 2024: 25 · 2023: 27 · 2022: 41 · 2021: 46 · 2020: 37 · 2019: 20 · 2018: 8 · 2014: 1
- FWCI
- 2.35
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- International Journal of Molecular Sciences (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Archivio Istituzionale della Ricerca - Università degli Studi dell Aquila (submittedVersion, public-domain)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- PubliCatt (Università Cattolica del Sacro Cuore) (submittedVersion, other-oa)
- Topics
- Health Sciences › Medicine › Epidemiology › Nonmelanoma Skin Cancer Studies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Hedgehog Signaling Pathway Studies
- Health Sciences › Medicine › Dermatology › Cancer and Skin Lesions
- Keywords
- basal cell carcinoma, tumor suppressor, proto-oncogenes, Hedgehog signaling, PTCH1, SMO, TP53, Ras family, UV-induced mutations, PTPN14, LATS1, Hippo signaling pathway, MYCN, TERT promoter mutation, carcinogenesis, targeted therapy
- MeSH terms
- Proto-Oncogene Mas, Animals, Basal Cell Carcinoma, Cell Transformation, Neoplastic, Humans, Mutation, Skin Neoplasms, Genetic Therapy, Signal Transduction, Biomarkers, Gene Expression Regulation, Neoplastic, Loss of Heterozygosity, Genetic Predisposition to Disease
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