An international group of scientists with the participation of researchers from Moscow State University named after M. V. Lomonosova found out which mutations are responsible for the formation of the most common type of skin cancer. The results of the work were published in the journal Nature Genetics.
Basal cell carcinoma (BC) is the most common and fifth most expensive type of cancer to treat (it accounts for up to 90% of all epithelial non-melanoma neoplasms). Risk factors include genetic disorders, the presence of freckles, X-rays and radioactive radiation, burns, and the use of drugs that suppress immunity (for example, in organ transplantation).
“In this study, an international team of authors found that in more than 80% of CD cases, it contains mutations in genes that lead to the formation of other types of cancer that were not previously associated with CD. This finding indicates the mechanisms of CD resistance to anticancer therapy and opens up opportunities for new clinical trials,”explains co-author Vladimir Seplyarsky, junior researcher at the Faculty of Bioengineering and Bioinformatics, Moscow State University. Lomonosov, Junior Researcher at the Molecular Evolution Sector of the Kharkevich Institute of the Russian Academy of Sciences.
Mutations in genes that are elements of the Sonic Hedgehog signaling pathway are hidden in 90% of basal cell carcinomas. These include the PTCH1 receptor and the SMO protein embedded in the cell membrane, which transmits the Hedgehog protein "command" to the Gli transcription factor to turn on protein synthesis from genes. Together with them, one of the causes of basal cell carcinoma in more than half of tumor cells is a “broken” version of the TP53 gene, which normally suppresses tumor formation and gives cells with defective DNA the order to “commit suicide” by apoptosis.
Scientists have compared mutations in basaliomas, melanomas, Wilson's tumors (kidney cancer, most often forming in the first or third year of life) and other types of cancer, in the occurrence of which the Sonic Hedgehog gene and its “accomplices” from the same signaling paths.
The results of the work showed that out of 387 genes on the "suspect list", several can actually contribute to the emergence of basal cell carcinoma and the development of tumor resistance to treatment. These include the genes that shape the Hippo-YAP pathway, not just the pathway controlled by the Sonic Hedgehog gene, which previously held almost all the burden of responsibility. Also, in the samples of basal carcinoma, the values for the content of the N-Myc protein were exceeded, which in this case was caused by a point mutation (replacement of one nucleotide - the “letter” of DNA) in the MB1 region. In other types of tumors, where the N-Myc protein in an increased concentration was “caught at the crime scene” earlier, this was caused by a mutation causing a multiple increase in the number of copies of the MYCN gene.
According to Vladimir Seplyarsky, “this work represents a turning point in understanding the molecular mechanisms of the emergence and development of basal carcinoma. Knowledge of the susceptibility of CD cells to oxidative stress may give rise to a different type of anticancer therapy for basal cell carcinoma. In addition, as the author of the study explained, the results of the work show which mutagens affect DNA damage in skin cells.