Abstract:
:Converging lines of evidence from varied scientific disciplines suggest that cutaneous melanomas comprise biologically distinct subtypes that arise through multiple causal pathways. Understanding the respective relationships of each subtype with etiologic factors such as UV radiation and constitutional factors is the first necessary step toward developing refined prevention strategies for the specific forms of melanoma. Furthermore, classifying this disease precisely into biologically distinct subtypes is the key to developing mechanism-based treatments, as highlighted by recent discoveries. In this review, we outline the historical developments that underpin our understanding of melanoma heterogeneity, and we do this from the perspectives of clinical presentation, histopathology, epidemiology, molecular genetics, and developmental biology. We integrate the evidence from these separate trajectories to catalog the emerging major categories of melanomas and conclude with important unanswered questions relating to the development of melanoma and its cells of origin.
journal_name
Pigment Cell Melanoma Resjournal_title
Pigment cell & melanoma researchauthors
Whiteman DC,Pavan WJ,Bastian BCdoi
10.1111/j.1755-148X.2011.00880.xsubject
Has Abstractpub_date
2011-10-01 00:00:00pages
879-97issue
5eissn
1755-1471issn
1755-148Xjournal_volume
24pub_type
杂志文章,评审abstract::Dyschromatosis symmetrica hereditaria (DSH) is a pigmentary genodermatosis caused by mutations in ADAR1. In this study, we performed mutation analysis on a family that included typical DSH patients. No mutations were found in any coding regions or exon-intron boundary regions of ADAR1, but a previously unreported non-...
journal_title:Pigment cell & melanoma research
pub_type: 杂志文章
doi:10.1111/pcmr.12863
更新日期:2020-07-01 00:00:00
abstract::Oncogenic BRAF and NRAS mutations drive human melanoma initiation. We used transgenic zebrafish to model NRAS-mutant melanoma, and the rapid tumor onset allowed us to study candidate tumor suppressors. We identified P38α-MAPK14 as a potential tumor suppressor in The Cancer Genome Atlas melanoma cohort of NRAS-mutant m...
journal_title:Pigment cell & melanoma research
pub_type: 杂志文章
doi:10.1111/pcmr.12925
更新日期:2020-09-10 00:00:00
abstract::Albinism is a rare genetic condition globally characterized by a number of specific deficits in the visual system, resulting in poor vision, in association with a variable hypopigmentation phenotype. This lack or reduction in pigment might affect the eyes, skin, and hair (oculocutaneous albinism, OCA), or only the eye...
journal_title:Pigment cell & melanoma research
pub_type: 杂志文章,评审
doi:10.1111/pcmr.12167
更新日期:2014-01-01 00:00:00
abstract::Melanins (eumelanin and pheomelanin) are synthesized in insects for several purposes including cuticle sclerotization and color patterning, clot formation, organogenesis, and innate immunity. Traditional views of insect immunity detail the storage of pro-phenoloxidases inside specialized blood cells (hemocytes) and th...
journal_title:Pigment cell & melanoma research
pub_type: 杂志文章,评审
doi:10.1111/pcmr.12590
更新日期:2017-07-01 00:00:00
abstract::The quantification of melanins is a complex task due to the chemical heterogeneity of the pigments and the difficulty of their isolation. The best accepted procedure currently consists in the chemical cleavage of melanins and the subsequent detection of degradation products by HPLC, which implies the destruction of sa...
journal_title:Pigment cell & melanoma research
pub_type: 杂志文章
doi:10.1111/pcmr.12140
更新日期:2013-11-01 00:00:00
abstract::Melanoma is the deadliest form of skin cancer; a primary driver of this high level of morbidity is the propensity of melanoma cells to metastasize. When malignant tumours develop distant metastatic lesions the new local tissue niche is known to impact on the biology of the cancer cells. However, little is known about ...
journal_title:Pigment cell & melanoma research
pub_type: 杂志文章
doi:10.1111/pcmr.12812
更新日期:2020-01-01 00:00:00
abstract::The aim of present study was to evaluate CD4(+) /CD8(+) ratio and CD4(+) CD25(hi) FoxP3(+) Tregs in GV patients with reference to their effect on disease onset and progression. Flow cytometry was used for determination of CD4(+) /CD8(+) ratio and Tregs in 82 patients and 50 controls. CD8(+) T-cell counts were signific...
journal_title:Pigment cell & melanoma research
pub_type: 杂志文章
doi:10.1111/pcmr.12105
更新日期:2013-07-01 00:00:00
abstract::Uveal melanoma (UVM) is the most common primary intraocular malignancy in adults. With over 50% of patients developing metastatic disease, there is an unmet need for improved diagnostic and therapeutic options. Efforts to understand the molecular biology of the disease have revealed several markers that correlate with...
journal_title:Pigment cell & melanoma research
pub_type: 杂志文章
doi:10.1111/pcmr.12810
更新日期:2020-01-01 00:00:00
abstract::RS-4-(4-Hydroxyphenyl)-2-butanol (rhododendrol, RD) was reported to induce leukoderma of the skin. To explore the mechanism underlying that effect, we previously showed that oxidation of RD with mushroom tyrosinase produces RD-quinone, which is converted to secondary quinone products, and we suggested that those quino...
journal_title:Pigment cell & melanoma research
pub_type: 杂志文章
doi:10.1111/pcmr.12363
更新日期:2015-05-01 00:00:00
abstract::PMEL is a pigment cell-specific protein responsible for the formation of fibrillar sheets within the pigment organelle, the melanosome. The fibrillar sheets serve as a template upon which melanins polymerize as they are synthesized. The PMEL fibrils are required for optimal pigment cell function, as animals that eithe...
journal_title:Pigment cell & melanoma research
pub_type: 杂志文章,评审
doi:10.1111/pcmr.12067
更新日期:2013-05-01 00:00:00
abstract::Hair pigmentation is one of the most conspicuous phenotypes in humans. Melanocytes produce two distinct types of melanin pigment: brown to black, indolic eumelanin and yellow to reddish brown, sulfur-containing pheomelanin. Biochemically, the precursor tyrosine and the key enzyme tyrosinase and the tyrosinase-related ...
journal_title:Pigment cell & melanoma research
pub_type: 杂志文章
doi:10.1111/j.1755-148X.2010.00755.x
更新日期:2011-02-01 00:00:00
abstract::Zebrafish respond to visual stimuli to adapt their body colour to the background. If, rather than being a simple on/off reaction to visual stimulation, the colour change involves cognitive and memory-related processes, training fish with cyclical changes of the background would be expected to increase its ability to c...
journal_title:Pigment cell & melanoma research
pub_type: 杂志文章
doi:10.1111/j.1755-148X.2008.00445.x
更新日期:2008-06-01 00:00:00
abstract::Melanoma incidence continues to rise at an alarming rate while effective systemic therapies remain very limited. Microphthalmia-associated transcription factor (MITF) is required for development of melanocytes and is an amplified oncogene in a fraction of human melanomas. Microphthalmia-associated transcription factor...
journal_title:Pigment cell & melanoma research
pub_type: 杂志文章
doi:10.1111/j.1755-148X.2008.00480.x
更新日期:2008-08-01 00:00:00
abstract::Defining markers of different phenotypic states in melanoma is important for understanding disease progression, determining the response to therapy, and defining the molecular mechanisms underpinning phenotype-switching driven by the changing intratumor microenvironment. The ABCB5 transporter is implicated in drug-res...
journal_title:Pigment cell & melanoma research
pub_type: 杂志文章
doi:10.1111/pcmr.12830
更新日期:2020-01-01 00:00:00
abstract::The Wnt/beta-catenin signaling pathway is involved in the melanocyte differentiation and melanoma development. However, the effect of beta-catenin for dendrite formation has not been clearly elucidated yet in normal human epidermal melanocytes (NHEM). To investigate the effect of beta-catenin, we transduced NHEM with ...
journal_title:Pigment cell & melanoma research
pub_type: 杂志文章
doi:10.1111/j.1755-148X.2010.00695.x
更新日期:2010-06-01 00:00:00
abstract::The neural crest is a transient structure in vertebrate embryos that generates multiple neural and mesenchymal cell types as well as melanocytes. Melanocytes in the skin either derive directly from neural crest cells populating the skin via a dorsolateral migratory pathway or arise by detaching from nerves innervating...
journal_title:Pigment cell & melanoma research
pub_type: 杂志文章,评审
doi:10.1111/j.1755-148X.2011.00834.x
更新日期:2011-06-01 00:00:00
abstract::Mutations within the OCA2 gene or the complete absence of the OCA2 protein leads to oculocutaneous albinism type 2. The OCA2 protein plays a central role in melanosome biogenesis, and it is a strong determinant of the eumelanin content in melanocytes. Transcript levels of the OCA2 gene are strongly correlated with pig...
journal_title:Pigment cell & melanoma research
pub_type: 杂志文章,评审
doi:10.1111/pcmr.12210
更新日期:2014-03-01 00:00:00
abstract::Metformin is the most widely used antidiabetic drug that belongs to the biguanide class. It is very well tolerated and has the major clinical advantage of not inducing hypoglycemia. Metformin decreases hepatic glucose production via a mechanism requiring liver kinase B1, which controls the metabolic checkpoint, AMP-ac...
journal_title:Pigment cell & melanoma research
pub_type: 杂志文章,评审
doi:10.1111/pcmr.12267
更新日期:2015-01-01 00:00:00
abstract::Ultraviolet radiation (UVR) can play two roles: induce cellular senescence and convert skin melanocytes into melanoma. To assess whether this conversion might rely on melanocytes having to first acquire a senescent phenotype, we studied the effects of physiological doses of UVR (UVA + UVB) on quiescent melanocytes in ...
journal_title:Pigment cell & melanoma research
pub_type: 杂志文章
doi:10.1111/pcmr.12888
更新日期:2020-09-01 00:00:00
abstract::One of the main advantages of using inducible and conditional transgenes to study pigment cell biology is that they allow for genetic manipulation within melanocytes after roles in general neural crest or melanoblast development have been fulfilled. Specifically, we focus here on the ability of the Tyr::CreER(T) ...
journal_title:Pigment cell & melanoma research
pub_type: 杂志文章
doi:10.1111/pcmr.12048
更新日期:2013-03-01 00:00:00
abstract::Normal cells possess a limited proliferative life span, after which they enter a state of irreversible growth arrest, called replicative senescence, which acts as a potent barrier against transformation. Transformed cells have escaped the process of replicative senescence and theoretically can not re-enter senescence....
journal_title:Pigment cell & melanoma research
pub_type: 杂志文章,评审
doi:10.1111/j.1755-148X.2010.00820.x
更新日期:2011-04-01 00:00:00
abstract::The deubiquitinating enzyme BAP1 is mutated in a hereditary cancer syndrome with a high risk of mesothelioma and melanocytic tumors. Here, we show that Bap1 deletion in melanocytes cooperates with the constitutively active, oncogenic form of BRAF (BRAFV600E ) and UV to cause melanoma in mice, albeit at very low freque...
journal_title:Pigment cell & melanoma research
pub_type: 杂志文章
doi:10.1111/pcmr.12735
更新日期:2019-03-01 00:00:00
abstract::Transcription factors initiate programs of gene expression and are catalysts in downstream molecular cascades that modulate a variety of cellular processes. Pax3 is a transcription factor that is important in the melanocyte and influences melanocytic proliferation, resistance to apoptosis, migration, lineage specifici...
journal_title:Pigment cell & melanoma research
pub_type: 杂志文章,评审
doi:10.1111/j.1755-148X.2008.00514.x
更新日期:2008-12-01 00:00:00
abstract::The complex genetic changes underlying metastatic melanoma need to be deciphered to develop new and effective therapeutics. Previously, genome-wide microarray analyses of human melanoma identified two reciprocal gene expression programs, including transcripts regulated by either transforming growth factor, beta 1 (TGF...
journal_title:Pigment cell & melanoma research
pub_type: 杂志文章
doi:10.1111/pcmr.12255
更新日期:2014-09-01 00:00:00
abstract::Many melanoma cells are resistant to the anti-proliferative effect of all trans retinoic acid (ATRA). Retinoic Acid Receptor-beta2 (RAR-beta2) mediates the ATRA growth inhibition. We found a correlation between the anti-proliferative activity of ATRA and expression of RAR-beta2. There was not a strict correlation betw...
journal_title:Pigment cell & melanoma research
pub_type: 杂志文章
doi:10.1111/j.1755-148X.2010.00702.x
更新日期:2010-06-01 00:00:00
abstract::The liver is the organ usually affected by metastatic uveal melanoma (MUM). Current treatments are almost always ineffective and mortality remains high. In this study, copy number variations (CNVs) were identified in 12 metastatic and five matched primary UMs (PUMs). Our data revealed a wide spectrum of genetic altera...
journal_title:Pigment cell & melanoma research
pub_type: 杂志文章
doi:10.1111/pcmr.12433
更新日期:2016-01-01 00:00:00
abstract::Human melanomas exhibit relatively high somatic mutation burden compared to other malignancies. These somatic mutations may produce neoantigens that are recognized by the immune system, leading to an antitumor response. By irradiating a parental mouse melanoma cell line carrying three driver mutations with UVB and exp...
journal_title:Pigment cell & melanoma research
pub_type: 杂志文章
doi:10.1111/pcmr.12591
更新日期:2017-07-01 00:00:00
abstract::We investigated the contributions of Tyrp1 and Gpnmb to the iris transillumination defect (TID) in five age cohorts of BXD mice. Using systems genetics, we also evaluated the role of other known pigmentation genes (PGs). Mapping studies indicate that Tyrp1 contributes to the phenotype at all ages, yet the TID maps to ...
journal_title:Pigment cell & melanoma research
pub_type: 杂志文章
doi:10.1111/pcmr.12106
更新日期:2013-07-01 00:00:00
abstract::BRAF inhibitors improve melanoma patient survival, but resistance invariably develops. Here we report the discovery of a novel BRAF mutation that confers resistance to PLX4032 employing whole-exome sequencing of drug-resistant BRAF(V600K) melanoma cells. We further describe a new screening approach, a genome-wide pigg...
journal_title:Pigment cell & melanoma research
pub_type: 杂志文章
doi:10.1111/pcmr.12197
更新日期:2014-03-01 00:00:00
abstract::Melanoma central nervous system metastases are increasing, and the challenges presented by this patient population remain complex. In December 2015, the Melanoma Research Foundation and the Wistar Institute hosted the First Summit on Melanoma Central Nervous System (CNS) Metastases in Philadelphia, Pennsylvania. Here,...
journal_title:Pigment cell & melanoma research
pub_type: 杂志文章,评审
doi:10.1111/pcmr.12538
更新日期:2016-11-01 00:00:00