Methylation variability and LINE-1 transcriptional activation in multiple myeloma.

Loss of DNA methylation in multiple myeloma leads to variable LINE-1 activation, with high L1 activity linked to increased proliferation and altered gene expression.

• Why it matters: Understanding epigenetic changes in multiple myeloma is crucial because they influence genome regulation and cancer progression, yet the mechanisms behind L1 activation remain unclear.
• What they did: Paired epigenome and transcriptome profiling of patient samples revealed that loss of DNA methylation creates variable partially methylated domains and correlates with increased L1 transcription, especially in high L1 activity cases.
• The result: High L1 activity associates with a proliferative, less differentiated state, suppression of immune pathways, and chimeric oncogene transcripts, suggesting epigenetic dysregulation promotes tumor growth and genome instability.