Project description:This SuperSeries is composed of the following subset Series: GSE28909: Genome wide analysis of acral melanoma (Illumina) GSE28910: Genome wide analysis of acral melanoma (Affymetrix) Refer to individual Series
Project description:Epigenetic signatures of alm and assoication with outcome. Background: Acral melanoma (AM) is a rare, aggressive type of cutaneous melanoma (CM) with a distinct genetic profile for which comprehensive genome-wide methylation analysis (GWMA) is lacking. We aimed to identify a methylome signature distinguishing primary acral lentiginous melanoma (PALM) from primary non-lentiginous AM involving the acral sites (NALM), metastatic ALM (MALM), primary non-acral CM (PCM), and acral nevus (AN). Methods: A total of 22 PALM, 9 NALM, 10 MALM, 9 PCM, and 3 AN cases were subjected to GWMA using the Illumina Infinium Methylation EPIC array interrogating 866,562 CpG sites, and their methylomes were compared. Results: A prominent finding was that the methylation profiles of PALM and NALM were distinct, although both are considered canonical AMs. Four of the genes most differentially methylated between PALM and NALM or PALM and MALM were HHEX, DIPK2A (formerly C3orf58), NELFB (formerly COBRA1), and TEF. However, when primary AMs (PALM+NALM) were compared with MALM, IFITM1 and SIK3 were the most differentially methylated, highlighting their pivotal role in the metastatic potential of AMs. Patients with NALM had significantly worse disease-specific (DSS) and overall survival than patients with PALM. Aberrant methylation was significantly associated with aggressive clinicopathologic parameters, including greater Breslow thickness, ulceration, increased mitotic rate, and lymph node metastasis, and with worse DSS. Conclusion: Our study emphasizes the importance of distinguishing the two epigenetically distinct subtypes of AM. We also identified novel epigenetic prognostic biomarkers that may serve to risk-stratify patients with AM. These epigenetic alterations may be leveraged for development of targeted therapies.
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:Genotyping of a matched normal, primary and metastatic acral melanoma DNA from blood and one matched Primary and one metastatic acral melanoma was genotyped on Affmetrix SNP6
Project description:Assessment of mutation on expression levels Transcriptomic profile of a matched primary and metastatic acral melanoma One Primary and one metastatic acral melanoma transcript expression were assayed (no matched normal)