背景:已知先天性黑素细胞痣(CMN)与镶嵌型NRAS或BRAF变体有关。然而,CMN中镶嵌变体的等位基因负荷与表型特征的确切相关性尚未确定。
目的:确定CMN的变异等位基因负荷与不同表型的相关性。
方法:选择Ras/Raf/MAPK信号通路中的一组基因用于110例CMN患者的测序。变异等位基因载量与临床表型的相关性,包括解剖定位,预计成人大小的病变,卫星,皮下结节,表面粗糙,颜色变化和多毛症,进行了分析。
结果:除了患者中主要的NRASp.Q61R/K(61.8%)和BRAFp.V600E变异(10%)外,我们还检测到NRAS的其他变体(p.G13R和p.M72fs),BRAF(第D22N)和MAP2K1(p。I107fs,p.F209fs,p.Q354H和p.G91_L92insHDQARRLVGDLEHKPSG)。此外,在CMN的躯干和四肢中发现了较高的NRASp.Q61R/K等位基因负荷。在CMN中也发现了更大的尺寸,更高的颜色变化和更显著的多毛症,表面粗糙和不对称。
结论:我们发现了更多的NRAS基因变异,BRAF和MAP2K1并建立了NRASp.Q61R/K等位基因载量与CMN中各种表型的相关性。除了临床实践中使用的表型或病理特征外,这项研究的发现可能有助于对CMN进行更准确和全面的分类。
BACKGROUND: Congenital melanocytic naevi (CMN) are known to be associated with mosaic NRAS or BRAF variants. However, the exact correlations of the allele load of mosaic variants in CMN with phenotypic characteristics have not been determined.
OBJECTIVE: To determine the correlation of variants allele load and different phenotypes of CMN.
METHODS: A panel of genes in the Ras/Raf/MAPK signalling pathway was selected for sequencing in 110 patients with CMN. Correlations between variant allele load and clinical phenotypes, including anatomical localization, projected adult size of the lesion, satellites, subcutaneous nodules, surface rugosity, colour variation and
hypertrichosis, were analysed.
RESULTS: In addition to the predominant NRAS p.Q61R/K (61.8%) and BRAF p.V600E variants (10%) in patients, we also detected additional variants of NRAS (p.G13R and p.M72fs), BRAF (p.D22N) and MAP2K1 (p.I107fs, p.F209fs, p.Q354H and p.G91_L92insHDQARRLVGDLEHHKPSG). Furthermore, a higher allele load of NRAS p.Q61R/K was found in the trunk and limbs of CMN. It was also found in CMN with larger size, higher colour variation and more significant
hypertrichosis, surface rugosity and asymmetry.
CONCLUSIONS: We discovered more genetic variants of NRAS, BRAF and MAP2K1 and established a correlation between the allele load of NRAS p.Q61R/K and various phenotypes in CMN. The findings of this study potentially facilitate a more accurate and comprehensive classification of CMN in addition to the phenotypic or pathological characteristics used in clinical practice.