Novel genetic alteration in congenital melanocytic nevus: MAP2K1 germline mutation with BRAF somatic mutation

Abstract

Congenital melanocytic nevus (CMN) represent a benign proliferative skin disease in the epidermis and dermis. CMN are historically known to be associated with activating NRAS or BRAF mutations. Melanoma frequently harbors the BRAF p.Val600Glu mutation, which is also commonly found in benign nevi. A recent study reported mutation of MAP2K1, a downstream effector of the RAS-RAF-MEK pathway, in melanoma with an overall frequency of 8%. Later, in 2019, Jansen P detected one activating MAP2K1 mutation in acral nevi. However, it is unknown whether MAP2K1 mutations are common in CMN, and how MAP2K1 contributes to the pathogenesis of CMN remains to be determined. In this study, we report one patient clinically and histologically diagnosed with CMN, with the MAP2K1 germline mutation and a BRAF p.Val600Glu somatic hit in the lesion. To the best of our knowledge, this is the first report of the coexistence of mutated BRAF and MAP2K1 in CMN, which may suggest that MAP2K1 mutations contribute to the occurrence and development of nevus expanding our knowledge of the genetics of CMN.

NRAS p.Q61R/K allele load is correlated to different phenotypes of congenital melanocytic naevi

“…7 Involvement of variants in other genes such as MAP2K1 and BRAF in CMN and a potential pathogenic potential to malignancy such as melanoma were recently indicated. [8][9][10] The correlations of genetic changes with phenotypic characteristics may be necessary for better understanding of the effect of genotype on clinical outcomes. 11 There have been several genotype-phenotype analyses reported previously, but the results are controversial.…”

“…A somatic variant in codon 61 of the tyrosine kinase gene NRAS accounts for 80% of large and giant CMN 7 . Involvement of variants in other genes such as MAP2K1 and BRAF in CMN and a potential pathogenic potential to malignancy such as melanoma were recently indicated 8–10 …”

Giant congenital melanocytic naevus with a novel CUX1–BRAF fusion mutation treated with trametinib

“…Vered Molho-Pessach iD , 1 Stav Hartshtark, 1 Sharon Merims, 2 Michal Lotem, 2 Nadia Caplan, 3 Hila Alfassi, 4 Alex Maly, 5 Gal Goldstein 6 and Rakefet Sidlik Muskatel 6 Departments of 1 Dermatology, 2 Oncology, 3 Radiology, 4 Plastic Surgery, 5 Pathology and 6 Pediatric Hematology-Oncology; Hadassah Medical Center, Hebrew University of Jerusalem, Faculty of Medicine, Jerusalem, Israel Email: rverem@hadassah.org.il Consensus on the clinical management of chronic radiation dermatitis and radiation fibrosis: a Delphi survey DOI: 10.1111/bjd.21852 DEAR EDITOR, Chronic radiation dermatitis and fibrosis (CRDF) has been defined as skin changes that develop more than 90 days after the cessation of radiation therapy. It encompasses dyspigmentation, epidermal thinning, dermal atrophy and telangiectasias.…”

“…A case report of MPXV treated with doxycycline for suspected rickettsial infection has been described in the literature, where the patient presented fever resolution within the first 24 h of treatment. 6 This clinical improvement could be explained by the natural evolution of the disease, by the antiinflammatory properties of doxycycline or by an unknown mechanism.…”

“…1 As already mentioned, GCMN result from postzygotic activating mutations in the MAPK pathway, interfering with the normal proliferation, differentiation and migration of melanoblasts and melanocytes. [2][3][4] The possibility of using MEK inhibitor treatment in selected GCMN cases has been suggested previously, 6 but to our knowledge, only one patient with GCMN (due to a AKAP9-BRAF fusion mutation) was treated with a MEK inhibitor, with encouraging results. 7 Our patient presented with a novel BRAF mutation (CUX1-BRAF), which has not been reported previously in GCMN.…”