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Noncoding Genes and Therapeutic Research in Basal Cell Carcinoma

By: Celeste L. Dixon
Posted: Wednesday, April 3, 2024

An expansive literature study has shed light on gene variants that may be associated with either protecting against or promoting the development of basal cell carcinoma. Ashley Wysong, MD, MS, of the University of Nebraska Medical Center, Omaha, and colleagues presented their work as a poster during the 2024 American Academy of Dermatology Association (AAD) Annual Meeting (Poster 52515).

Noncoding RNAs provide important potential routes for intervention, the team noted, “as has [already] been investigated with [small interfering] RNAs and mimics.” The genes they identified as most significant involved pigmentation (23 variants) and cytoskeletal or motility pathways (60 variants), and of these genes, 75.6% occurred in introns or intergenic regions. Their resources included Embase and Medline; the National Human Genome Research Institute–European Bioinformatic Institute’s Genome-Wide Associative Studies (GWAS) catalogue; RefSeq (the National Center for Biotechnology Reference Sequence Database); dbSNP (the Single Nucleotide Polymorphism Database); and Ensembl (the genome browser for vertebrate genomes).

Dr. Wysong and co-investigators highlighted 10 of the most significant single nucleotide polymorphisms (SNPs), and 5 promoted basal cell carcinoma and 5 protected against it. The associated genes for the five promotion SNPs are IRF4, RCC2, NOX4, TYR, BNC2, CLPTM1L, and MIR4457. For the five protective SNPs, the associated genes are TGM3, CASP8, LINC00709 and LINC02676, RGS22, and CDKN2B-AS1.

The identification of these pathways “demonstrates a network of GWAS-significant differences in basal cell carcinoma that could help target [this cancer] more effectively. CASP8, for example, involved in the apoptosis pathways…, demonstrates a protective SNP, rs10931936-C, explained the researchers. More work, they suggested, could investigate “therapies promoting CASP8, such as tazarotene, a topical antitumor retinoid.”

Disclosure: No disclosure information for the study authors was provided.

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