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| Status |
Public on Mar 08, 2023 |
| Title |
Longitudinal gene expression profiling identifies a poor risk subset of patients with ABC-type Diffuse Large B Cell Lymphoma |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Despite the effectiveness of immuno-chemotherapy, 40% of patients with diffuse large B-cell lymphoma (DLBCL) experience relapse or refractory disease. Longitudinal studies have previously focused on the mutational landscape of relapse but falling short of providing a consistent relapse-specific genetic signature. In our study, we have focussed attention on the changes in gene expression profile accompanying DLBCL relapse using archival paired diagnostic/relapse specimens from 38 de novo DLBCL patients. Cell of origin remained stable from diagnosis to relapse in 80% of patients, with only a single patient showing COO switching from ABC to GCB. Analysis of the transcriptomic changes that occur following relapse suggest ABC and GCB relapses are mediated via different mechanisms. We developed a 30-gene discriminator for ABC-DLBCLs derived from relapse-associated genes, that defined clinically distinct high and low risk subgroups in ABC-DLBCLs at diagnosis in datasets comprising both population-based and clinical trial cohorts. This signature also identified a population of <60-year-old patients with superior PFS and OS treated with Ibrutinib-R-CHOP as part of the PHOENIX trial. Altogether this new signature adds to the existing toolkit of putative genetic predictors now available in DLBCL that can be readily assessed as part of prospective clinical trials.
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| Overall design |
Gene expression profiels for 76 paired diagnosis and relapse DLBCL biopsies from 38 patients were generated using the Ion AmpliSeq™ Human Gene Expression assay.
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| Contributor(s) |
Bewicke-Copley F, Korfi K, Araf S, Hodkinson B, Kumar E, Cummin T, Ashton-Key M, Barrans S, Van Hoppe S, Burton C, Elshiekh M, Rule S, Crosbie N, Clear A, Calaminici M, Runge H, Hills RK, Scott DW, Rimsza LM, Menon G, Sha C, Davies J, Nagano A, Davies A, Painter D, Smith A, Gribben J, Naresh KN, Westhead DR, Okosun J, Steele A, Hodson DJ, Balasubramanian S, Johnson P, Wang J, Fitzgibbon J |
| Citation(s) |
35947123 |
| Submission date |
Jan 12, 2022 |
| Last update date |
Jun 07, 2023 |
| Contact name |
Findlay Bewicke-Copley |
| E-mail(s) |
f.copley@qmul.ac.uk
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| Organization name |
Centre for Molecular Oncology, Barts Cancer Institute, Queen Mary University of London
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| Street address |
John Vane Science Centre, Barts Cancer Institute
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| City |
London |
| ZIP/Postal code |
EC1M 6BQ |
| Country |
United Kingdom |
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| Platforms (1) |
| GPL17303 |
Ion Torrent Proton (Homo sapiens) |
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| Samples (76)
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| Relations |
| BioProject |
PRJNA796606 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE193566_RAW.tar |
6.5 Mb |
(http)(custom) |
TAR (of TXT) |
| GSE193566_all_batchCorrectedCounts.txt.gz |
5.6 Mb |
(ftp)(http) |
TXT |
| GSE193566_all_rawCounts.txt.gz |
1.9 Mb |
(ftp)(http) |
TXT |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
| Processed data are available on Series record |
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