Atypical spindle cell/pleomorphic lipomatous tumors harbor TP53 deletions in contrast with conventional spindle cell lipomas

Abstract

BackgroundAtypical spindle cell/pleomorphic lipomatous tumor (ASPLT) is a benign adipocytic neoplasm. A definitive diagnosis is often challenging due to the overlap of clinicopathological features with spindle cell lipoma and, to a lesser extent, with atypical lipomatous tumor. Our aim was to investigate the value of DNA methylation profiling and copy number analysis in distinguishing ASPLT from its mimickers.DesignWe collected a pilot cohort of ASPLTs (n = 7) and spindle cell lipomas (n = 8) with available formalin-fixed paraffin-embedded or fresh frozen tumor tissue. Genome-wide DNA methylation and copy number variation data were generated using the Illumina Infinium MethylationEPIC v2.0 BeadChips. DNA methylation patterns of ASPLTs were compared with other adipocytic tumors, including ordinary lipomas (n = 14), spindle cell lipomas (n = 23), atypical lipomatous tumors/well-differentiated liposarcomas (n = 21), dedifferentiated liposarcomas (n = 25), pleiomorphic liposarcomas (n = 19), and myxoid liposarcomas (n = 24).ResultsUnsupervised clustering and dimensionality reduction (Uniform Manifold Approximation and Projection) revealed that ASPLTs did not form a distinct DNA methylation class but partially clustered with spindle cell lipomas and well-differentiated/dedifferentiated liposarcomas. Copy number profiling showed deletions of 13q14, encompassing RB1, in four ASPLTs (57%) and deletions of TP53 in five cases (71%), compared with no loss of TP53 in spindle cell lipomas and MDM2 amplification in well-differentiated liposarcomas. Additional methylation and copy number alteration data of extra samples will follow soon.ConclusionsOur preliminary results indicate that copy number profiling of regions encompassing TP53, MDM2, and RB1, rather than methylation profiling, may be used as an additional diagnostic tool to distinguish ASPLT from spindle cell lipoma.BackgroundAtypical spindle cell/pleomorphic lipomatous tumor (ASPLT) is a benign adipocytic neoplasm. A definitive diagnosis is often challenging due to the overlap of clinicopathological features with spindle cell lipoma and, to a lesser extent, with atypical lipomatous tumor. Our aim was to investigate the value of DNA methylation profiling and copy number analysis in distinguishing ASPLT from its mimickers.DesignWe collected a pilot cohort of ASPLTs (n = 7) and spindle cell lipomas (n = 8) with available formalin-fixed paraffin-embedded or fresh frozen tumor tissue. Genome-wide DNA methylation and copy number variation data were generated using the Illumina Infinium MethylationEPIC v2.0 BeadChips. DNA methylation patterns of ASPLTs were compared with other adipocytic tumors, including ordinary lipomas (n = 14), spindle cell lipomas (n = 23), atypical lipomatous tumors/well-differentiated liposarcomas (n = 21), dedifferentiated liposarcomas (n = 25), pleiomorphic liposarcomas (n = 19), and myxoid liposarcomas (n = 24).ResultsUnsupervised clustering and dimensionality reduction (Uniform Manifold Approximation and Projection) revealed that ASPLTs did not form a distinct DNA methylation class but partially clustered with spindle cell lipomas and well-differentiated/dedifferentiated liposarcomas. Copy number profiling showed deletions of 13q14, encompassing RB1, in four ASPLTs (57%) and deletions of TP53 in five cases (71%), compared with no loss of TP53 in spindle cell lipomas and MDM2 amplification in well-differentiated liposarcomas. Additional methylation and copy number alteration data of extra samples will follow soon.ConclusionsOur preliminary results indicate that copy number profiling of regions encompassing TP53, MDM2, and RB1, rather than methylation profiling, may be used as an additional diagnostic tool to distinguish ASPLT from spindle cell lipoma.C