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Molecular profiling of pediatric mature B-cell lymphoma treated in population-based prospective clinical trials

ABSTRACT: The spectrum of entities, the therapeutic strategy and the outcome of mature aggressive B-cell lymphomas (maB-NHL) differs between children and adolescents on the one hand and adult patients on the other. Whereas adult maB-NHL have been studied in detail, data on molecular profiling of pediatric maB-NHL are hitherto lacking. Our aim was to characterize pediatric maB-NHL on the molecular level and to evaluate whether a molecular diagnosis of pediatric maB-NHL reveals clinically relevant groups. Keywords: pediatric disease state analysis

ORGANISM(S): Homo sapiens

PROVIDER: GSE10172 | GEO | 2008/06/17

SECONDARY ACCESSION(S): PRJNA108377

REPOSITORIES: GEO

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Project description:Identification of blood biomarkers that prospectively predict progression of Mycobacterium tuberculosis infection to tuberculosis disease might lead to interventions that combat the tuberculosis epidemic. We aimed to assess whether global gene expression measured in whole blood of healthy people allowed identification of prospective signatures of risk of active tuberculosis disease. RESULTS:Between July 6, 2005, and April 23, 2007, we enrolled 6363 from the ACS study and 4466 from independent South African and Gambian cohorts. 46 progressors and 107 matched controls were identified in the ACS cohort. A 16 gene signature of risk was identified. The signature predicted tuberculosis progression with a sensitivity of 66Â·1% (95% CI 63Â·2â68Â·9) and a specificity of 80Â·6% (79Â·2â82Â·0) in the 12 months preceding tuberculosis diagnosis. The risk signature was validated in an untouched group of adolescents (p=0Â·018 for RNA sequencing and p=0Â·0095 for qRT-PCR) and in the independent South African and Gambian cohorts (p values <0Â·0001 by qRT-PCR) with a sensitivity of 53Â·7% (42Â·6â64Â·3) and a specificity of 82Â·8% (76Â·7â86) in 12 months preceding tuberculosis. Interpretation: The whole blood tuberculosis risk signature prospectively identified people at risk of developing active tuberculosis, opening the possibility for targeted intervention to prevent the disease. In this prospective cohort study, we followed up healthy, South African adolescents aged 12â18 years from the adolescent cohort study (ACS) who were infected with M tuberculosis for 2 years. We collected blood samples from study participants every 6 months and monitored the adolescents for progression to tuberculosis disease. A prospective signature of risk was derived from whole blood RNA sequencing data by comparing participants who developed active tuberculosis disease (progressors) with those who remained healthy (matched controls). After adaptation to multiplex qRT-PCR, the signature was used to predict tuberculosis disease in untouched adolescent samples and in samples from independent cohorts of South African and Gambian adult progressors and controls. Participants of the independent cohorts were household contacts of adults with active pulmonary tuberculosis disease.

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Molecular profiling of pediatric mature B-cell lymphoma treated in population-based prospective clinical trials

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