Melanoma

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Melanoma
Melanoma malignum on the left leg of a 60-year-old woman
ICD-10 C43
ICD-9 172
ICD-O: Template:ICDO
OMIM 155600
DiseasesDB 7947
MedlinePlus 000850
eMedicine derm/257 

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Melanoma Microchapters

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Patient Information

Overview

Historical Perspective

Classification

Pathophysiology

Causes

Differentiating Melanoma from other Diseases

Epidemiology and Demographics

Risk Factors

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Natural History, Complications and Prognosis

Diagnosis

Diagnostic Study of Choice

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Overview

History

Epidemiology

The incidence of melanoma has increased in the recent years, but it is not clear to what extent changes in behavior, in the environment, or in early detection are involved.[1]

Causes

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Pathophysiology

Diagnosis

History and Symptoms | Physical Examination | Staging | Lab Tests | Electrocardiogram | X Ray | MRI | CT | Echocardiography | Other imaging findings | Other diagnostic studies

Treatment

Treatment of advanced malignant melanoma is performed from a multidisciplinary approach including dermatologists, medical oncologists, radiation oncologists, surgical oncologists, general surgeons, plastic surgeons, neurologists, neurosurgeons, otorhinolaryngologists, radiologists, pathologists/dermatopathologists, research scientists, nurse practitioners and physician assistants, and palliative care experts. Nurse practitioners (NPs) and physician assistants (PAs) are qualified to evaluate and treat patients on behalf of their supervising physicians. Treatment guidelines can be found through many resources available to health care professionals around the world. Inspired by melanoma’s increasing prevalence, researchers are seeking to understand the pathways that regulate melanin production.

Medical therapy | Surgical options | Primary prevention | Secondary prevention | Financial costs | Future therapies

Future thought

One important pathway in melanin synthesis involves the transcription factor MITF. The MITF gene is highly conserved and is found in people, mice, birds, and even fish. MITF production is regulated via a fairly straightforward pathway. UV radiation causes increased expression of transcription factor p53 in keratinocytes, and p53 causes these cells to produce melanoctye stimulating hormone (MSH), which binds to MC1R receptors on melanocytes. Ligand-binding at MC1R receptors activates adenyl cyclases, which produce cAMP, which activates CREB, which promotes MITF expression. The targets of MITF include p16 (a CDK inhibitor) and Bcl2, a gene essential to melanocyte survival. It is often difficult to design drugs that interfere with transcription factors, but perhaps new drugs will be discovered that can impede some reaction in the pathway upstream of MITF.

Studies of chromatin structure also promise to shed light on transcriptional regulation in melanoma cells. It has long been assumed that nucleosomes are positioned randomly on DNA, but murine studies of genes involved in melanin production now suggest that nucleosomes are stereotypically positioned on DNA. When a gene is undergoing transcription, its transcription start site is almost always nucleosome-free. When the gene is silent, however, nucleosomes often block the transcriptional start site, suggesting the nucleosome position may play a role in gene regulation.

Finally, given the fact that tanning helps protect skin cells from UV-induced damage, new melanoma prevention strategies could involve attempts to induce tanning in individuals who would otherwise get sunburns. Redheads, for example, do not tan because they have MC1R mutations. In mice, it has been shown that the melanin-production pathway can be rescued downstream of MC1R. Perhaps such a strategy will eventually be used to protect humans from melanoma.

References

  1. Berwick M, Wiggins C. "The current epidemiology of cutaneous malignant melanoma". Front Biosci. 11: 1244–54. PMID 16368510.

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