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Reading which genes were switched on in 240 lymphoma samples sorted one disease into three, and the group whose cells looked like a particular stage of normal B-cell development lived the longest.
Alizadeh and Staudt had shown in 2000 that diffuse large B-cell lymphoma is not one disease. Rosenwald and the Lymphoma/Leukemia Molecular Profiling Project turned that into a survival predictor. Biopsy samples from 240 patients were profiled on DNA microarrays and analysed for genomic abnormalities; subgroups were defined by hierarchical clustering, and a risk predictor was built on 160 patients and tested on the remaining 80.
Three gene-expression subgroups came out: germinal-centre B-cell-like, activated B-cell-like, and type 3. The two commonest oncogenic events in the disease, the BCL2 translocation and c-rel amplification, were found only in the germinal-centre group, which also had the highest five-year survival. Searching for individual genes whose expression tracked survival produced four signatures, reflecting germinal-centre B cells, proliferating cells, the reactive stromal and immune cells of the lymph node, and the major histocompatibility complex class II complex. Seventeen of those genes were assembled into a predictor of overall survival after chemotherapy, which was independent of the International Prognostic Index.
The stromal and immune signatures are the part that aged best: they anticipated by a decade the idea that what surrounds the tumour predicts outcome as strongly as what is in it.
The reason a pathology report on diffuse large B-cell lymphoma says germinal-centre or non-germinal-centre, and the origin of every attempt since to treat the two differently. It also made the case that microarray profiling could do something the clinical index could not, which is what pulled genomics into haematology.
The practical form of cell-of-origin classification, used in pathology laboratories worldwide. When a report says germinal-centre or non-germinal-centre, this is almost always the algorithm behind it.
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Shares Louis M. Staudt, Confirmation of the molecular classification of diffuse large B-cell lymphoma by immunohistochemistry using a tissue microarray, BCL6, Genetics and pathogenesis of diffuse large B-cell lymphoma and the tag lymphoma-evidence.
Shares International Prognostic Index (IPI), BCL6, Genetics and pathogenesis of diffuse large B-cell lymphoma, Cell of origin (GCB vs ABC) and the tag lymphoma-evidence.
Shares Genetics and pathogenesis of diffuse large B-cell lymphoma, Cell of origin (GCB vs ABC), BCL-2, Biomarkers are not validated or standardised and the tag lymphoma-evidence.
Shares Confirmation of the molecular classification of diffuse large B-cell lymphoma by immunohistochemistry using a tissue microarray, Genetics and pathogenesis of diffuse large B-cell lymphoma, Cell of origin (GCB vs ABC), Biomarkers are not validated or standardised and the tag lymphoma-evidence.
Shares International Prognostic Index (IPI), Lymphoma roadmap: from a jaw tumour in Uganda and the first human cancer virus to gene-expression subtypes, PET-adapted chemotherapy, CAR-T cells, bispecific antibodies and the genetics-directed trials now recruiting, National Cancer Institute (NIH), Diffuse large B-cell lymphoma and the tag lymphoma-evidence.
Shares Genetics and pathogenesis of diffuse large B-cell lymphoma, Cell of origin (GCB vs ABC), Lymphoma roadmap: from a jaw tumour in Uganda and the first human cancer virus to gene-expression subtypes, PET-adapted chemotherapy, CAR-T cells, bispecific antibodies and the genetics-directed trials now recruiting, Diffuse large B-cell lymphoma and the tag lymphoma-evidence.
Shares Cell of origin (GCB vs ABC), Biomarkers are not validated or standardised, Lymphoma roadmap: from a jaw tumour in Uganda and the first human cancer virus to gene-expression subtypes, PET-adapted chemotherapy, CAR-T cells, bispecific antibodies and the genetics-directed trials now recruiting, Diffuse large B-cell lymphoma and the tag lymphoma-evidence.
Shares Cell of origin (GCB vs ABC), Biomarkers are not validated or standardised, Lymphoma roadmap: from a jaw tumour in Uganda and the first human cancer virus to gene-expression subtypes, PET-adapted chemotherapy, CAR-T cells, bispecific antibodies and the genetics-directed trials now recruiting, Diffuse large B-cell lymphoma and the tag lymphoma-evidence.