Eruptive Melanocytic Nevi: A Review

Burian, Ewa Anna; Jemec, Gregor B. E.

doi:10.1007/s40257-019-00444-8

Cited by 23 publications

(35 citation statements)

References 105 publications

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“…A single mutation -BRAF V600E -drives temporary proliferation followed by subsequent growth arrest, but the mechanisms that underlie this bi-phasic phenotype remain opaque. Equally perplexing is the conditional nature of growth arrest induction, wherein incompletely excised nevi can regrow to their former dimensions (17), or established nevi can erupt in response to external stimuli (18). The mechanisms that permit these events are as ambiguous as nevogenesis itself and require that the growth-arrest phenotype be both recurrently plastic and durable.…”

Section: Discussionmentioning

confidence: 99%

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BRAF^V600Einduces reversible mitotic arrest in human melanocytes via microRNA-mediated suppression of AURKB

McNeal

Belote

Zeng

et al. 2020

Preprint

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Benign melanocytic nevi commonly form when melanocytes that acquire a BRAFV600E mutation undergo a period of rapid proliferation and subsequent arrest. Constitutive activation of MAPK signaling downstream of BRAF drives the initial proliferative phenotype. However, the factors that establish and maintain growth arrest in nevi remain elusive. The growth-arrested state of BRAFV600E melanocytes is not conferred by additional genetic mutations, suggesting a role for regulatory elements. We investigated the role of microRNAs in the initiation and maintenance of nevus arrest. Using primary human melanocytes, melanocytic nevi, and adjacent melanoma, we show that MIR211-5p and MIR328-3p are enriched in nevi compared to normal melanocytes, then subsequently downregulated in adjacent melanoma. Both MIR211-5p and MIR328-3p proved necessary effectors of BRAFV600E-induced growth arrest in human melanocytes. We identified microRNA target networks which, when suppressed, phenocopy BRAFV600E-induced arrest and converge on inhibition of AURKB to block cell cycle progression in primary human melanocytes.Statement of SignificanceWe describe a microRNA regulatory network that enforces BRAFV600E-induced growth arrest in human melanocytes during melanocytic nevus formation. De-regulation of MIR211-5p and MIR328-3p targets – which converge on AURKB – leads to cell cycle re-entry and melanoma progression. AURKB inhibition therefore provides a potential therapeutic intervention for melanoma prevention or treatment.

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Section: Discussionmentioning

confidence: 99%

“…Interestingly, the growth restraint itself is non-permanent. Outside the context of transformation, nevus melanocytes can also re-enter the cell cycle following exposure to specific stimuli, as seen in cases of recurrent nevi (17) or widespread nevus eruption (18).…”

mentioning

confidence: 99%

BRAF^V600Einduces reversible mitotic arrest in human melanocytes via microRNA-mediated suppression of AURKB

McNeal

Belote

Zeng

et al. 2020

Preprint

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“…EMN lesions appear within a short period, usually weeks or months after the drug use. However, they may occur after several years 10 . According to the literature, EMN induced by anti‐TNF‐α agents appear within a few weeks or months.…”

Section: Discussionmentioning

confidence: 99%

“…EMN lesions are commonly observed in sun‐exposed areas, such as the trunk and extremities. However, the involvement of sun‐protected areas, such as the palms and soles, has been reported to be 45%, especially after immunosuppressive therapy 10 . The cases of relationship anti‐TNF‐α agents, in all trunk or extremities lesions, and, in three, accompanying palm and sole lesions were reported.…”

Section: Discussionmentioning

confidence: 99%

Eruptive melanocytic nevi during etanercept treatment in an ankylosing spondylitis patient: Case report

Erdem

Altunay

Özkur

2020

Dermatologic Therapy

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Eruptive melanocytic nevi (EMN) are rare multiple melanocytic lesions that rare and associated with dermatological and systemic diseases. Drug induced EMN is also reported with the use of biological or nonbiological chemotherapeutics, immunosuppressive agents, and melanocyte stimulators. In recent years, the increasing use of biological drugs resulted in an increased reports of EMN induced by these drugs. The objective of this abstract is reporting EMN in a patient receiving etanercept treatment. In addition, we also present a literature review of the previously cases with anti‐tumor necrosis factor‐α biological agents.

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“…They more likely have dermal mitoses and there is a trend toward increased Ki-67 proliferation index (Chan et al, 2010;Martins-Costa et al, 2019). The sudden occurrence of new nevi has been reported in association with blistering diseases, immunosuppressive therapy, chemotherapy and immunodeficiency (Burian et al, 2019). Dermoscopic surveillance of nevi show that 31-69% of nevi may change over time (Braun et al, 1998;Kittler et al, 2000;Haenssle et al, 2010).…”

Section: Growth In Nevimentioning

confidence: 99%

Identification and clinical evaluation of senescence-associated markers to distinguish melanocytic nevi from melanomas

Orfanidis

2020

Linköping University Medical Dissertations

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Melanoma is a form of cancer that develops in melanocytes. While it represents only 5% of skin malignancies, it is the most aggressive and lethal. Benign proliferation of these cells form the melanocytic nevi. The definitive diagnosis of melanocytic nevi or melanoma lesions is histopathologic. However, it is estimated that a correct diagnosis is established by means of standard skin biopsy in only 83% of the melanocytic lesions; of the remaining cases 8% and 9% are overinterpreted (false positives) and under-interpreted (false negatives), respectively. This underscores the importance of additional diagnostic tests. Since cellular senescence is considered to be a tumor suppressive mechanism, immuno-histochemistry using senescence markers has been suggested for the evaluation of difficult melanocytic lesions; however, the routinely used senescence markers lack the ability to distinguish nevi from melanoma. The general aim of this thesis is therefore to identify novel senescence markers that may aid in melanoma diagnosis.In study I, we established a cellular model with nevus-mimicking characteristics consisting in primary melanocytes that become senescent. Transcriptomic analysis allowed expanding the set of senescence-associated markers that could distinguish nevi from melanoma and identifying tubulin β-3 as a potential diagnostic marker. Depletion of tubulin β-3 and pretreatment with tubulin destabilizing drugs in melanocytes and melanoma cells induced a senescence-like phenotype in vitro. In particular, reduced migration capacity and induction of cell cycle arrest in G2/M phase of the cell cycle was demonstrated.In study II, a potential inter-cellular signaling pathway between melanoma cells and stromal fibroblasts, that might facilitate melanoma invasion, was investigated. Ultraviolet (UV) radiation was shown, both in melanoma cells and fibroblasts, to promote the release and activation of TGF-β1 and subsequent increase in expression of the serine protease FAP-α, a protein that plays role in extracellular matrix degradation and therefore facilitates the invasion of melanoma cells. Such mechanism was not functional in senescent melanocytes.In study III, it was shown that tubulin β-3 immunostaining aids in the diagnosis of nevi and melanomas. The diagnostic criterium was the tubulin β-3 gradient within the melanocytic nevi that was no longer apparent in melanoma. Different patterns of tubulin β-3 immunostaining in melanoma were described, dermoscopy-immunohistochemistry associations were found, specific dermoscopic features highlighted, and the prognostic value of this tubulin β-3 marker was examined. The progression rate in patients whose melanomas had areas with loss of tubulin β-3 was 4 times higher than in patients without this feature, although statistical significance could not be reached (p=0.06).In conclusion, transcriptomic analysis expanded the set of senescence-associated markers that could distinguish nevi from melanoma and identified tubulin β-3 as novel immunohistochemistry marker shown to have diagn...

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Eruptive Melanocytic Nevi: A Review

Cited by 23 publications

References 105 publications

BRAF^V600Einduces reversible mitotic arrest in human melanocytes via microRNA-mediated suppression of AURKB

BRAF^V600Einduces reversible mitotic arrest in human melanocytes via microRNA-mediated suppression of AURKB

Eruptive melanocytic nevi during etanercept treatment in an ankylosing spondylitis patient: Case report

Identification and clinical evaluation of senescence-associated markers to distinguish melanocytic nevi from melanomas

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Eruptive Melanocytic Nevi: A Review

Cited by 23 publications

References 105 publications

BRAFV600Einduces reversible mitotic arrest in human melanocytes via microRNA-mediated suppression of AURKB

BRAFV600Einduces reversible mitotic arrest in human melanocytes via microRNA-mediated suppression of AURKB

Eruptive melanocytic nevi during etanercept treatment in an ankylosing spondylitis patient: Case report

Identification and clinical evaluation of senescence-associated markers to distinguish melanocytic nevi from melanomas

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BRAF^V600Einduces reversible mitotic arrest in human melanocytes via microRNA-mediated suppression of AURKB

BRAF^V600Einduces reversible mitotic arrest in human melanocytes via microRNA-mediated suppression of AURKB