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

Author:

Zemtsov Alexander12ORCID

Affiliation:

1. University Dermatology Center Muncie Indiana USA

2. Department of Dermatology Indiana University School of Medicine Indianapolis Indiana USA

Abstract

AbstractObjectivePatients 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.MethodsTo report new research elucidating the etiology of melanoma, BCC, MMD‐induced cancers, and potentially other environmentally induced malignancies.ResultsDysregulation 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.ConclusionThe 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.

Publisher

Wiley

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