Table 1 Main studies using high-throughput approaches for the molecular classification and prognostic stratification of lymphoproliferative diseases
From: Integrative systems medicine approaches to identify molecular targets in lymphoid malignancies
# of patients/disease type | Platform | Main finding(s) | Clinical implication(s) | Reference(s) |
|---|---|---|---|---|
414 DLBCL | GEP (Affymetrix U133 plus 2.0 microarrays) | Stromal-1 and stromal-2 signatures | Stromal-1 associated with better outcome | [14] |
203 DLBCL | Array CGH; GEP (Affymetrix U133 plus 2.0 microarrays) | Three molecular subtypes (GCB, ABC, PMBL) | Two MCRs restricted to ABC-DLBCLs predict adverse survival | [13] |
127 DLBCL | Sequencing (Illumina GAIIx and HiSeq 2000) | 109 genes with clear evidence of somatic mutation | Post-transcriptional modifications of histones act as core driver events in NHL | [16] |
6 DLBCL (discovery); 73 biopsies (screening) | Massively parallel sequencing; WES; copy number analysis | Alterations of chromatin-modifying enzymes and genes involved in immune recognition by T cells | Drugs targeting pathways selectively disrupted in DLBCL subtypes | [17] |
140 DLBCL | Genomewide DNA methylation profiling | Methylation disruption is a main epigenetic event | Extent of methylation variability is associated with survival outcomes | [19] |
Various types of mature B-NHL, including FL, Burkitt lymphoma, marginal-zone lymphoma and CLL | Sequencing and mutation analysis | Inactivation of CREBBP/EP300 represents a common event in FL and DLBCL | Rationale for the use of histone deacetylase inhibitors in B-NHL | [18] |
893 DLBCL | GEP; tissue microarrays | One-third of DLBCL demonstrate MYC/BCL2 coexpression | MYC/BCL2 coexpression more common in ABC-DLBCL and associated with aggressive clinical course | [24] |
10 FL | WGS; WES | Early driver mutations in chromatin regulator genes (CREBBP, EZH2 and MLL2); mutations in EBF1 and regulators of NF-κB signaling (MYD88 and TNFAIP3) gained at transformation | Therapies targeting genetic alterations in a common progenitor clone are attractive | [44] |
1274 CLL | Mutational and cytogenetic analysis | Four prognostic subgroups (high-risk, harboring TP53 and/or BIRC3 abnormalities; intermediate-risk, harboring NOTCH1 and/or SF3B1 mutations and/or del11q22-q23; low-risk, harboring 12 or a normal genetics; and very low-risk, harboring del13q14 only) | Differences in 10-year survival (29 % for group 1; 37 % for group 2; 57 % for group 3 and 69.3 % for group 4) | [48] |