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BCAT1 and miR-2504: novel methylome signature distinguishes spindle/desmoplastic melanoma from superficial malignant peripheral nerve sheath tumor

ABSTRACT: BCAT1 and miR-2504: novel methylome signature distinguishes spindle/desmoplastic melanoma from superficial malignant peripheral nerve sheath tumor

PROVIDER: PRJNA445606 | ENA |

REPOSITORIES: ENA

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BCAT1 and miR-2504: novel methylome signature distinguishes spindle/desmoplastic melanoma from superficial malignant peripheral nerve sheath tumor

Project description:Genome wide methylation of superficial malignant peripheral nerve sheath tumors and spindle cell melanomas. EPIC HD 850K array is used to identifiy differentally methylated promoter region probes and unique methyome signatures. Superficial/cutaneous malignant peripheral nerve sheath tumor (c-MPNST) is a rare, soft tissue neoplasm that shares morphological, immunohistochemical and molecular with spindle and desmoplastic melanoma (SDM). Herein we investigate a methylome signature distinguishing between both entities. DNA from formalin-fixed, paraffin-embedded (FFPE) tissues was extracted and processed using the Illumina Infinium epic array interrogating 866,562 CpG sites. Using a home grown informatics pipeline we identify differentially methylated regions (DMR) between both entities. Functional network analysis for enrichment signatures was performed using DAVID tools. Identified DMR’s are compared with TCGA skin cutaneous melanoma (SKCM) data and a recently published set of MPNST in order to assess specifity of the identified signature. Thirty patients are included (SDM= 15 and c-MPNST=15) including 23 males and 7 females. Unsupervised hierarchical clustering probes showed a distinct pattern of methylation between c-MPNST and SDM. Two probes cg20783223 and cg13332552 co-localized in the promoter region of BCAT1 and MIR2504. Pathway analysis highlighted an enrichment in s subset of genes involved in breast and gastric cancer centered on BCAT1 and downstream activated genes in the mTORC pathway. Our study identifies BCAT1 as a unique marker distinguishing between SDM and MPNST. Further immunohistochemical studies are underway to investigate the role of BCAT expression in that regard.

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