From Bedside to Genetic Analysis: New Insights into Pathophysiology of Melanoma, Basal Cell Carcinoma, and Other Cancers

Overview

Journal Skin Res Technol

Specialty Biomedical Engineering

Date 2024 Jun 28

PMID 38937899

Authors

Alexander Zemtsov

Affiliations

Soon will be listed here.

Abstract

Objective: Patients with myotonic muscular dystrophy (MMD) were observed to have numerous basal cell carcinoma (BCC) and abnormal dysplastic nevi (DN) on non-sun exposed skin. Simultaneously a large study published in the Journal of American Medical Association (JAMA) illustrated that patients with MMD have "overall" an increased risk for cancer development. Based on these findings, this author in 2010 postulated that dysregulation of RNA binding proteins (RBP), responsible for clinical manifestations of MMD, is also responsible for the development of BCC and melanoma.

Methods: To report new research elucidating the etiology of melanoma, BCC, MMD-induced cancers, and potentially other environmentally induced malignancies.

Results: Dysregulation of RBP induces aberrant mRNA splicing; recent data indicates that abnormal mRNA splicing not just plays a key role in the pathogenesis of melanoma but is a hallmark of essentially all human malignancies.

Conclusion: The author's hypothesis is that ultraviolet (UV) radiation induces DNA damage in intronic regions of a variety of genes. Furthermore, these UV-induced abnormal DNA dimers, repeats and mutations interfere with normal mRNA splicing thus producing abnormal proteins. These abnormal proteins in turn activate oncogenic pathways such as hedgehog, MAP kinase, and WNT.

Citing Articles

Skin Cancer Knowledge, Sun Exposure, Photoprotection Behavior, and Perceived Barriers Associated with Skin Cancer Types in a Greek Cohort: A Cross-Sectional Study on the Island of Crete.

Koumaki D, Evangelou G, Gregoriou S, Kouloumvakou S, Manios A, Katoulis A Cancers (Basel). 2025; 16(24.

PMID: 39766125 PMC: 11726760. DOI: 10.3390/cancers16244226.

From bedside to genetic analysis: New insights into pathophysiology of melanoma, basal cell carcinoma, and other cancers.

Zemtsov A Skin Res Technol. 2024; 30(7):e13832.

PMID: 38937899 PMC: 11211085. DOI: 10.1111/srt.13832.

References

Chi L, Lam S . Structural roles of CTG repeats in slippage expansion during DNA replication. Nucleic Acids Res. 2005; 33(5):1604-17. PMC: 1065260. DOI: 10.1093/nar/gki307. View

Zemtsov A . From bedside to genetic analysis: New insights into pathophysiology of melanoma, basal cell carcinoma, and other cancers. Skin Res Technol. 2024; 30(7):e13832. PMC: 11211085. DOI: 10.1111/srt.13832. View

Gadalla S, Lund M, Pfeiffer R, Gortz S, Mueller C, Moxley 3rd R . Cancer risk among patients with myotonic muscular dystrophy. JAMA. 2011; 306(22):2480-6. PMC: 3286183. DOI: 10.1001/jama.2011.1796. View

Gajos-Michniewicz A, Czyz M . WNT Signaling in Melanoma. Int J Mol Sci. 2020; 21(14). PMC: 7402324. DOI: 10.3390/ijms21144852. View

Zampetti A, Silvestri G, Manco S, Khamis K, Masciullo M, Bianchi M . Dysplastic nevi, cutaneous melanoma, and other skin neoplasms in patients with myotonic dystrophy type 1: a cross-sectional study. J Am Acad Dermatol. 2014; 72(1):85-91. DOI: 10.1016/j.jaad.2014.09.038. View

Hussein M, Wood G . hMLH1 and hMSH2 gene mutations are present in radial growth-phase cutaneous malignant melanoma cell lines and can be induced further by ultraviolet-B irradiation. Exp Dermatol. 2004; 12(6):872-5. DOI: 10.1111/j.0906-6705.2003.00104.x. View

Munoz M, Perez Santangelo M, Paronetto M, Mata M, Pelisch F, Boireau S . DNA damage regulates alternative splicing through inhibition of RNA polymerase II elongation. Cell. 2009; 137(4):708-20. DOI: 10.1016/j.cell.2009.03.010. View

Itin P, Laeng R . [Multiple pigmented basalioma of the scalp in a patient with Curschmann-Steinert myotonia dystrophica. Confirmation of a rare symptom constellation]. Hautarzt. 2001; 52(3):244-6. DOI: 10.1007/s001050051298. View

Wang Y, Pfeiffer R, Alsaggaf R, Meeraus W, Gage J, Anderson L . Risk of skin cancer among patients with myotonic dystrophy type 1 based on primary care physician data from the U.K. Clinical Practice Research Datalink. Int J Cancer. 2017; 142(6):1174-1181. PMC: 5773358. DOI: 10.1002/ijc.31143. View

10.

Ravanat J, Douki T, Cadet J . Direct and indirect effects of UV radiation on DNA and its components. J Photochem Photobiol B. 2001; 63(1-3):88-102. DOI: 10.1016/s1011-1344(01)00206-8. View

11.

DAmbrosio E, Gonzalez-Perez P . Cancer and Myotonic Dystrophy. J Clin Med. 2023; 12(5). PMC: 10004154. DOI: 10.3390/jcm12051939. View

12.

Hu J, Adebali O, Adar S, Sancar A . Dynamic maps of UV damage formation and repair for the human genome. Proc Natl Acad Sci U S A. 2017; 114(26):6758-6763. PMC: 5495279. DOI: 10.1073/pnas.1706522114. View

13.

Mueller C, Hilbert J, Martens W, Thornton C, Moxley 3rd R, Greene M . Hypothesis: neoplasms in myotonic dystrophy. Cancer Causes Control. 2009; 20(10):2009-20. PMC: 3110730. DOI: 10.1007/s10552-009-9395-y. View

14.

Sinha R, Hader D . UV-induced DNA damage and repair: a review. Photochem Photobiol Sci. 2003; 1(4):225-36. DOI: 10.1039/b201230h. View

15.

Mao P, Smerdon M, Roberts S, Wyrick J . Chromosomal landscape of UV damage formation and repair at single-nucleotide resolution. Proc Natl Acad Sci U S A. 2016; 113(32):9057-62. PMC: 4987812. DOI: 10.1073/pnas.1606667113. View

16.

Rastogi R, Richa , Kumar A, Tyagi M, Sinha R . Molecular mechanisms of ultraviolet radiation-induced DNA damage and repair. J Nucleic Acids. 2011; 2010:592980. PMC: 3010660. DOI: 10.4061/2010/592980. View

17.

Zemtsov A . Association between basal, squamous cell carcinomas, dysplastic nevi and myotonic muscular dystrophy indicates an important role of RNA-binding proteins in development of human skin cancer. Arch Dermatol Res. 2009; 302(3):169-70. DOI: 10.1007/s00403-009-0997-8. View

18.

Stieler W, Plewig G . [Multiple basaliomas in Curschmann-Steinert myotonia atrophica]. Hautarzt. 1986; 37(4):226-9. View

19.

Chen W, Geng D, Chen J, Han X, Xie Q, Guo G . Roles and mechanisms of aberrant alternative splicing in melanoma - implications for targeted therapy and immunotherapy resistance. Cancer Cell Int. 2024; 24(1):101. PMC: 10926661. DOI: 10.1186/s12935-024-03280-x. View