{"database":"ENA","file_versions":[],"scores":null,"additional":{"omics_type":["Genomics"],"center_name":["University of Nebraska Medical Center"],"full_dataset_link":["https://www.ebi.ac.uk/ena/browser/view/PRJNA1132266"],"scientific_name":["Homo sapiens"],"long_description":["Mantle cell lymphoma (MCL) is a genetically and clinically heterogeneous B-cell malignancy. We study two MCL cohorts with differing treatment patterns: one enriched for immunochemotherapy, the other for chemotherapy alone. TP53 alterations are consistently associated with poor prognosis, whereas ATM mutations correlate with improved outcomes following rituximab-based chemotherapy. Based on recurrent genetic events, six clusters are identified and refined into three prognostic groups: high-risk (TP53 mutations and deletions at 17p13.3, 13q14.2, and 19p13.3), intermediate-risk (ATM and epigenetic regulator mutations, or gains at 8q/17q/15q), and low-risk (lacking TP53 alterations, rare ATM mutations without 11q deletions, gains at 3q, deletions at 6q). Transcriptomic analysis reveals enrichment of proliferation, metabolism-promoting gene signatures in high-risk angiogenesis and NOTCH signaling in intermediate-risk and proinflammatory-related (i.e., IFNα, TNFα) in low-risk MCLs. Multi-proteomic spatial profiling using imaging mass cytometry (IMC) demonstrates enrichment of CD4⁺ T cells with high expression of exhaustion markers and dominant population of myeloid cells skewed toward an M2-like phenotype. Spatially, TP53-perturbed MCLs are immune infiltrated but exhausted, while ATM-perturbed cases remain immune-cold with dense tumor. Functional analysis shows that p53 represses BCR signaling through PTPN6 activation. Collectively, these findings highlight distinct molecular and immune landscapes and reveal therapeutic vulnerabilities in high-risk TP53-perturbed MCL. Overall design: R273C and R248Q mutations of TP53 were created in TP53-wt MCL cell line Z-138. The isogenic pairs were treated with AMG-232 for 24 hours to activate p53, followed by Cut&Run analysis. Dox-inducible wt-TP53 was introduced into TP53-deficient MCL cell lines Marver-1 and Mino. The isogenic pairs were treated with Dox for 12h, followed by Cut&Run analysis."],"repository":["ENA"],"additional_accession":[]},"is_claimable":false,"name":"Functional genomics and tumor microenvironment analysis reveal prognostic biological subtypes in Mantle cell lymphoma","description":"Functional genomics and tumor microenvironment analysis reveal prognostic biological subtypes in Mantle cell lymphoma","dates":{"last_updated":"2025-09-24","first_public":"2025-09-08"},"accession":"PRJNA1132266","cross_references":{"GEO":["GSE271594"],"taxon":["9606"]}}