User talk:Clicker1234/sandbox

Background about the biological mechanisms of melanoma:

Information: Tumors originate in melanocytes, and cancerous growths develop when unprepared DNA damage to skin cells (most often caused by UV radiation) triggers mutations that lead to the skin cells multiplying rapidly to form malignant tumors. Melanocytes are neural-crest originating cells that migrate to the skin (and other sites) early during fetal development. They reside mainly in the basal layer of the epidermis and synthesize melanin. Melanoma develops from a series of distinct stages. It has been proven that changes in the expression of specific proteins is what causes the deregulated control of the skin microenvironment. In early stages, it can be cured by surgical resection. But once it has become metastatic it is very hard to treat and often becomes fatal. --Evolmed469 (talk) 04:46, 29 February 2016 (UTC)

Primary sources: K. Satyamoorthy & M. Herlyn (2002) Cellular and Molecular Biology of Human Melanoma, Cancer Biology & Therapy, 1:1, 14-17, DOI: 10.4161/cbt.1.1.32 --Evolmed469 (talk) 04:46, 29 February 2016 (UTC)

Secondary sources: http://www.cancernetwork.com/articles/malignant-melanoma-biology-diagnosis-and-management --Evolmed469 (talk) 04:46, 29 February 2016 (UTC)

http://www.skincancer.org/skin-cancer-information/melanoma--Evolmed469 (talk) 04:46, 29 February 2016 (UTC)

Evolutionary work that has been done on melanoma:

There is still an ongoing research to find the exact order of occurrence of pathogenic mutations in melanoma, yet it is still not clear which order they follow. One possible hypothesis is that Melanoma genetically evolved from precursor Lesions. To test this, they sequenced 293 genes that are mostly present in cancer cells in 150 sides of 37 precursor lesions located adjacent to primary melanomas. The lesion’s sides are benign, intermediate lesions and invasive melanomas. The results from this experiment suggest that mutations of genes that activate the mitogen-activated protein kinase pathway initiate precursor lesions. Unequivocally benign lesions sheltered BRAF V600E mutations, whereas intermediate lesions were enriched for NRAS mutations. 77% sides of intermediate lesions and melanomas in situ harbored TERT promoter mutations. A study suggests that early stage of the neoplastic progression promotes selection of these mutations. Biallelic inactivation of CDKN2A emerged exclusively in invasive melanomas. PTEN and TP53 mutations were found only in advanced primary melanomas. The point-mutation burden increased from benign through intermediate lesions to melanoma, with a strong signature of the effects of ultraviolet radiation detectable at all evolutionary stages. Copy-number alterations became prevalent only in invasive melanomas. Tumor heterogeneity became apparent in the form of genetically distinct subpopulations as melanomas progressed. From the obtained results, scientists came up with progressive succession of genetic alterations during melanoma trajectory which suggests different evolutionary pathways for various melanoma subtypes. The presence of multiple pathogenic genetic alteration and several histopathological features characterize an intermediate category of melanocytic neoplasia. The evolutionary implication of this study include ultraviolet radiation as a major factor in both the initiation and progression of melanoma disorder.

Primary Source: From the Departments of Dermatology and Pathology (A.H.S., I.Y., E.T., A.G., J.N., L.P., B.R., B.C.B.) and the Helen Diller Family Comprehensive Cancer Center (A.H.S., I.Y., E.T., A.G., B.C.B.), University of California, San Francisco (UCSF), San Francisco; the Departments of Dermatology and Pathology, Cleveland Clinic, Cleveland (I.K.); the Department of Pathology, Orlando Health, Orlando, FL (A.S.); the Department of Dermatology, University Hospital of Zurich, Zurich, Switzerland (R.D.); and the Department of Dermatology, Dorset County Hospital, Dorchester (C.D.), and the Department of Dermatology, St. John’s Institute of Dermatology, London (W.R., A.R.) — both in the United Kingdom.

http://apps.webofknowledge.com/full_record.do?product=WOS&search_mode=GeneralSearch&qid=2&SID=3FvuYGgSmx6bBrkLlda&page=1&doc=8--Evolmed469 (talk) 15:41, 1 March 2016 (UTC)

Secondary source for this study: http://www.nejm.org/doi/full/10.1056/NEJMoa1502583 — Preceding unsigned comment added by Shima sahra (talk • contribs) 07:40, 29 February 2016 (UTC)

Information: "The ability of melanoma cells to invade and metastasize to distant organs in the body suggests its adaptability to varying microenvironment."--Evolmed469 (talk) 04:46, 29 February 2016 (UTC)

Primary sources:

Secondary sources:

Discussions of what is already in wikipedia and what is not:

The definition and causes of melanoma is already on wikipedia. So are statistics. Biology (pathophysiology) is quite detailed. It does mention "The rate 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" --> might be able to find something that touches on this comment? There is also no talk about the evolutionary biology/aspect of melanoma. We should be able to add a section on this with all new information/research.--Evolmed469 (talk) 04:52, 29 February 2016 (UTC)

Dark Skin to Protect Against Melanoma
In a study published in Proceeding of the Royal Society B, Mel Greaves, states possibility that dark skin may have evolved to protect against Melanoma. She argues that about 1.2 million years ago, black pigmentation became an essential adaption and led to a natural selection that favored colored skin. Melanin provides filter for UV radiation which is the main factor that causes skin cell to become cancerous cell. This argument is supported by studying albinos in Africa that they illustrate what might have been the impact of UVR on early humans. This research revealed that skin cancer played a part in skin color and that we were originally white then evolved to black about a million years ago, then some went back to white as they migrated away from Africa.

Primary Source: http://rspb.royalsocietypublishing.org/content/281/1781/20132955.full

Secondary Source: http://news.nationalgeographic.com/news/2014/03/140307-skin-color-cancer-evolution-albinos-africa/ — Preceding unsigned comment added by Clicker1234 (talk • contribs) 04:08, 1 March 2016 (UTC)