Project description:We performed microRNA sequencing of primary human FFPE Acral Melanoma (AM), Cutaneous Melanoma (CM), Acral Nevi (AN), and Cutaneous Nevi (CN). We found that previously identified ratios of microRNAs, particularly miR-21-5p and miR-211-5p, were able to accurately classify benign and malignant melanocytic neoplasia, both in non-acral cutaneous melanomas and nevi (CM vs CN), as well as matched acral melanoma and nevi (AM vs AN). Receiver operating characteristic area under the curve (AUC) of Ensemble models trained using these microRNA ratios demonstrated AUCs of 0.88-0.90 across these melanoma subtypes, suggesting the potential utility of these ratios as a biomarker of malignancy in melanocytic neoplasia.
Project description:The study included 15 patients (7 males, 8 females) with JMML. Peripheral blood and/or bone marrow aspirates were collected on EDTA at diagnosis. Non-hematopoietic tissues (fibroblasts) was derived from skin biopsy for each patient. Exome sequencing was performed in several distinct series between 2012 and 2017, which explains the differences in capture kit versions and reference genome version.Targeted enrichment and massive parallel sequencing were performed on paired genomic DNA from leukocytes and fibroblasts. Exome capture was carried out using the SureSelect Human All Exon V4+UTRs or V5 or V5+UTRs or SureSelect Clinical Research (Agilent Technologies, Santa Clara, CA, USA) according to manufacturer’s instruction and protocols by IntegraGen (Evry, France). Paired-end 75 bases sequencing was performed on a HiSeq2000 or HiSeq4000 instrument (Illumina, San Diego, CA, USA). Image analysis and base calling were performed using the Real Time Analysis (RTA) pipeline v. 1.14 (Illumina) with default parameters. The alignment of paired-end reads to the reference human genome (UCSC GRCh37/hg19 or UCSC GRCh38), variant calling and generation of Quality variants scores were carried out using the CASAVA v.1.8 pipeline (Illumina).
Project description:Congenital melanocytic nevi (CMN) and common acquired melanocytic nevi (AMN) are skin conditions that result from an excess of melanocytes arising during fetal development or detected postnatally. Appropriately weighted whole-genome methylation analysis can be used as a basis for further research in dermatopathology and, in this application, provides new insights into nevus biology.
Project description:The purpose of this study was to comprehensively study and compare the molecular gene expression profiles of common melanocytic nevi (GSE53223), dysplastic nevi (GSE53223), and primary melanoma.
Project description:Human CD4+ T cells mediate spontaneous rejection of acquired benign melanocytic nevi, in the majority of cases, through a break in peripheral tolerance. For the remaining cases, nevi remain stable and do not progress to malignancy. In this experiment, we compared gene expression of post-transplant rejected nevi to stable nevi in order to better characterize their transcriptional profiles.
Project description:Acquired melanocytic nevi grow and persist in a stable form into adulthood. Using genome-wide methylation profiling, we evaluated 32 histopathologically confirmed, and dermoscopically characterized nevi, with matched adjacent skin, to identify key epigenetic regulatory mechanisms involved in nevogenesis. Benign (n=13; 69% globular and 31% non-specific dermoscopic pattern) and dysplastic (n=19; 95% reticular/nonspecific dermoscopic pattern) nevi were dissimilar with only two shared differentially methylated (DM) loci. Relative to adjacent skin, benign nevi demonstrated an increase in both genome-scale methylation and methylation of Alu/LINE-1 retrotransposable elements, a marker of genomic stability, as well as global methylation. In contrast, dysplastic nevi showed evidence for genomic instability via hypomethylation of Alu/LINE-1. The difference in methylation between benign and dysplastic nevi was statistically significant for Alu (P = 0.00019) and LINE-1 (P = 0.000035) retrotransposable elements. Using dermoscopic classifications, reticular/nonspecific nevi had 59,572 CpG DM loci (Q < 0.05), whereas globular nevi had non-significant DM loci. The relative activity of reticular/non-specific nevi was evidenced by 50,720 hypomethylated loci being enriched for accessible chromatin, and 8,852 hypermethylated loci strongly enriched, for example, marks of active gene promoters, which suggests that gain of DNA methylation observed in these nevus types plays a role in gene regulation.
Project description:WES/WGS sequencing data of 37 germline runs, which were uploaded to umbrella studies. The sequencing was always paired. The WGS sequencing was on HiSeq X Ten using the Illumina TruSeq DNA Nano Kit. The WES Sequencing was on HiSeq4000 with Agilent Sureselect V5+UTR.