Multi-omics analysis of HLTF context-dependent regulation across TCGA cohorts revealed its potential as new biomarker in tumour

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Abstract
The SNF2-family Helicase-Like Transcription Factor (HLTF) has been implicated in tumorigenesis, with evidence suggesting both tumour-suppressive and oncogenic functions. To clarify the nature of this increasingly emerging double function, we analysed the full HLTF’s alterome across TCGA cohorts combining first gene expression with genomic and epigenomic layers of de-regulation, and investigating further their determinants through the integration of DNA methylation profiles - both at promoter-proximal and distal regions, the copy-number alterations, and all somatic mutations. This multi-layered analysis highlighted specific context-dependent HLTF’s regulatory configurations across human cancers, even modulated by either dosage effects or loss-of-function events. The clinical relevance of HLTF’s alterations, identified through tumour-specific associations with patient outcomes, supports its potential as new biomarker in cancer overall.

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