Genetic Variants In Congenital Melanocytic Nevus In East Asia
Ren Cai, M.D.1,2, Yi Sun, M.D.2, Yun Zou, M.D.2.
1Bio-X Institute, Shanghai Jiao Tong University, Shanghai, China, 2Shanghai Ninth People's Hospital, Shanghai Jiao Tong University, Shanghai, China.
PURPOSE: Congenital melanocytic nevi, the benign proliferative diseases related epidermis and dermis, are associated with differing phenotypic manifestations. The study of correlation between gene mutations and phenotype may uncover previously unknown relationships. In this study, somatic mutations present in congenital melanocytic nevi were identified by using targeted next-generation sequencing.
METHODS: In a single-center cohort study, 22 fresh congenital melanocytic nevi tissue and blood specimen from minimal biopsies performed at Shanghai Ninth People's Hospital were obtained and underwent sequencing across a panel of vascular anomalies, congenital melanocytic nevi and melanoma. Somatic and germline mutations were curated by excluding variants that were presumed to be of low mapping quality. We identified the mutation variants, and the correlation between of mutation variants with clinical growth pattern.
RESULTS: Among the 22 patients CMN, in 12 males and 10 females with the mean age of 5.16 years (SD, 2.81). The head/neck was the most common anatomical site (n=19, 86.4%), followed by extremity (3, 13.6%). The mean size of nevus lesion was 12 cm (SD, 10.08). Somatic mutations such as NRAS (N=14), BRAF(N=1), KRAS(N=1), and MAP2K1(N=2), and germline mutations in EPHB4(N=5), RASA1(N=2), ACVRL1(N=1) were detected. Nevus with higher NRAS mutation frequency harbored higher color variation (F=23.51, P=0.0004, 95% CI=82.46-217.0). For color distribution, the mean mutation frequency in uniform nevus was 25.6% (SD, 4.6) while 16.0% (SD, 6.8) in ununiform nevus (p=0.0088). As for thickness, the mean mutation frequency in no thickness was 14.9% (SD, 5.9) while 24.8% (SD, 6.4) patients with thickening nevi (p=0.0219). All patient with germline mutations in EPHB4 and RASA1together with patients with MAP2K1 somatic mutation showed irregular boundary.
CONCLUSIONS: In this study, according to genotype and phenotype of Congenital melanocytic nevi, we put forward our hypothesis that mutation frequency of NRAS could be the predictor of clinical growth pattern of CMN, and there may be some correlations with CMN and vascular anomalies such as CM-AVM and HHT.
Back to 2020 Posters