Spatiotemporal expression of NRAS and occurrence of giant congenital melanocytic nevi

Abstract

The mechanism underlying giant congenital melanocytic nevus (GCMN) formation is not fully understood. According to recent research, NRAS gene mutation is the main driving factor in GCMN. Melanocytic precursor cells proliferate during the embryonic stage after acquiring NRAS mutations. However, why GCMN undergoes intense proliferation in the embryonic stage and then stops postnatally remains unknown. The current theory for this phenomenon is that the GCMN undergoes oncogene‐induced senescence. However, there is not enough evidence to indicate that senescence induces growth arrest in GCMN. In this study, we hypothesized that the expression level of the NRAS gene changes dynamically during the development and differentiation of neural crest cells into melanocytes and that the NRAS expression level determines whether the cell proliferates or becomes quiescent.

Association of novel MUC16, MAP3K15 and ABCA1 mutation with giant congenital melanocytic nevus

“…By screening, we identified four significantly mutated genes, and NRAS, MUC16, ABCA1 and MAP3K15. In our results, the NRAS gene mutation was consistent with those reported previously [ 6 , 16 ]. This result validates the important role of this gene in the development of GCMN, and we will not discuss it in depth here.…”

“…Therefore, clarification of GCMN genetic alterations can improve the accuracy of clinical diagnosis and assessment of the risk of malignant transformation. A current study suggests that the formation of GCMN is directly associated with NRAS gene mutations, which leads to sustained activation of the mitogen-activated protein kinase (MAPK) pathway and promotion of melanophore proliferation [ 6 ]. Nevertheless, there is no evidence that the high rate of malignant transformation in GCMN is closely associated with NRAS mutations [ 7 ].…”

Establishment and characterization of an immortalized human giant congenital melanocytic nevi cell line

“…This hypothesis is consistent with the results of the present study. At the same time, we also put forward a hypothesis that mature and differentiated giant nevus cells may reduce the transcription of NRAS, thereby reducing activation of the MAPK pathway (Aimaier et al, 2022). However, the mechanism requires further investigation.…”

A clinical and biologic review of congenital melanocytic nevi

“…22,23 Recently, Aimaier et al proposed a new hypothesis for this phenomenon. 24 They hypothesized that the expression level of the NRAS gene fluctuates dynamically during the development and differentiation of neural crest cells into melanocytes. 24,25 Specifically, the authors speculated that NRAS is expressed at a high level during the neural crest cell stage, and thereby NRAS gene mutations result in increased MAPK pathway activation and cell proliferation.…”

“…Recently, Aimaier et al. proposed a new hypothesis for this phenomenon 24 . They hypothesized that the expression level of the NRAS gene fluctuates dynamically during the development and differentiation of neural crest cells into melanocytes 24,25 .…”