TY - JOUR
T1 - BCAT1 and miR-2504
T2 - novel methylome signature distinguishes spindle/desmoplastic melanoma from superficial malignant peripheral nerve sheath tumor
AU - Jour, George
AU - Vasudevaraja, Varshini
AU - Prieto, Victor G.
AU - Snuderl, Matija
AU - Torres-Cabala, Carlos A.
AU - Al-Rohil, Rami
AU - Sulman, Erik P.
AU - Ballester, Leomar Y.
AU - Aung, Phyu P.
N1 - Publisher Copyright:
© 2018, United States & Canadian Academy of Pathology.
PY - 2019/3/1
Y1 - 2019/3/1
N2 - Superficial/cutaneous malignant peripheral nerve sheath tumor is a rare soft tissue neoplasm that shares morphological, immunohistochemical, and molecular features with spindle/desmoplastic melanoma. We aimed to identify a methylome signature to distinguish these two entities. We analyzed 15 cases of spindle/desmoplastic melanoma and 15 cases of cutaneous malignant peripheral nerve sheath tumor in 23 men and 7 women. DNA from formalin-fixed, paraffin-embedded tissues was extracted and processed using the Illumina Infinium Methylation EPIC array interrogating 866,562 CpG sites. Using a home-grown informatics pipeline, we identified differentially methylated positions between the two entities. Functional network analysis for enrichment signatures was performed using DAVID tools. Identified differentially methylated positions were compared with the Cancer Genome Atlas’s cutaneous melanoma dataset and a recently published malignant peripheral nerve sheath tumor dataset to assess the specificity of the identified signature. Unsupervised hierarchical clustering showed different patterns of methylation in cutaneous malignant peripheral nerve sheath tumor and spindle/desmoplastic melanoma. Two probes, cg20783223 and cg13332552, colocalized in the promoter region of BCAT1 and miR-2504. Pathway analysis highlighted enrichment in a subset of genes involved in breast and gastric cancer centered on BCAT1 and downstream activated genes in the mTOR pathway. Our study identifies BCAT1 as a novel methylome signature distinguishing spindle/desmoplastic melanoma from cutaneous malignant peripheral nerve sheath tumor.
AB - Superficial/cutaneous malignant peripheral nerve sheath tumor is a rare soft tissue neoplasm that shares morphological, immunohistochemical, and molecular features with spindle/desmoplastic melanoma. We aimed to identify a methylome signature to distinguish these two entities. We analyzed 15 cases of spindle/desmoplastic melanoma and 15 cases of cutaneous malignant peripheral nerve sheath tumor in 23 men and 7 women. DNA from formalin-fixed, paraffin-embedded tissues was extracted and processed using the Illumina Infinium Methylation EPIC array interrogating 866,562 CpG sites. Using a home-grown informatics pipeline, we identified differentially methylated positions between the two entities. Functional network analysis for enrichment signatures was performed using DAVID tools. Identified differentially methylated positions were compared with the Cancer Genome Atlas’s cutaneous melanoma dataset and a recently published malignant peripheral nerve sheath tumor dataset to assess the specificity of the identified signature. Unsupervised hierarchical clustering showed different patterns of methylation in cutaneous malignant peripheral nerve sheath tumor and spindle/desmoplastic melanoma. Two probes, cg20783223 and cg13332552, colocalized in the promoter region of BCAT1 and miR-2504. Pathway analysis highlighted enrichment in a subset of genes involved in breast and gastric cancer centered on BCAT1 and downstream activated genes in the mTOR pathway. Our study identifies BCAT1 as a novel methylome signature distinguishing spindle/desmoplastic melanoma from cutaneous malignant peripheral nerve sheath tumor.
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U2 - 10.1038/s41379-018-0146-z
DO - 10.1038/s41379-018-0146-z
M3 - Article
C2 - 30310175
AN - SCOPUS:85054827937
SN - 0893-3952
VL - 32
SP - 338
EP - 345
JO - Modern Pathology
JF - Modern Pathology
IS - 3
ER -