Track

Clinical Studies

Abstract

Unbalanced copy number alterations (CNA) are an important finding assisting in melanoma diagnosis. Herein, we investigate detection of CNA using methylation arrays EPIC 900V2. 10 unequivocal melanomas (Group 1: primary n=5, metastatic n=5) previously tested with a 607 gene panel (matched tumor/normal, DNA panel) are included along with 4 non-melanomas (Group 2). For the latter category, correlation with FISH, RNA seq (126 gene fusion panel) and/or SNP microarray data was performed. All cases were analyzed using EPIC 900k V2; CNA was performed using lg2FC 0.25 for hemizygous loss and 0.50 for homozygous loss. Tumor purity averaged 50%. C-MYC amplification (8q) was identified in 9/10 cases, homozygous CDKN2a loss (9p21) was identified in 8/10 cases, RREB1 gain (6p) in 7/10 cases, MYB loss (6q) in 3/10 cases, and only one case out of 10 had CCND1 amplification. All of these events were concordant with CNA calls from NGS analysis. Some whole arm chromosomal loss and gains were detected on methylation analysis solely. Within Group 2, no aneuploidy was identified in the aforementioned genes. Methylation showed 100%, 100%, and 72% concordance with NGS/FISH/SNP arrays in primary melanomas, non-melanomas, and metastatic melanomas, respectively. Our results show that methylation array is a promising technique for genomic aneuploidy detection in melanoma diagnosis. Further validation on larger cohorts is underway.