Proteogenomic Features Define Novel Subtypes of Mantle Cell Lymphoma

Introductions Recent advancements in mass spectrometry-based proteomics have unveiled novel translational and post-translational aspects of tumor biology. The joint characterization of tumor proteomics with genomics and transcriptomics enables proteogenomic analysis, improving our understanding of the molecular mechanisms, identifying new proteome-specific markers associated with clinical outcomes, and discovering novel treatment approaches. However, proteogenomic features remain largely uncharted due to a scarcity of information on MCL proteome. Methods We conducted a proteogenomic profiling study with 4 normal and 27 MCL B cells derived from healthy donors and MCL patients, integrating whole-exon sequencing (WES), transcriptome sequencing and mass spectrometry-based proteomics with data-independent acquisition (DIA) mode. We assessed the relationship among genetic lesions, RNA and protein expression, and further classified MCL based on omics information using k-means clustering. Results To this end, we first identified 1107 differentially expressed proteins between MCL and normal B cells (FDR