Analysis of the coding genome of diffuse large B-cell lymphoma
Laura Pasqualucci,Vladimir Trifonov,Giulia Fabbri,Jing Ma,Davide Rossi,Annalisa Chiarenza,Victoria A. Wells,Adina Grunn,Monica Messina,Oliver Elliot,Joseph M. Chan,Govind Bhagat,Amy Chadburn,Gianluca Gaidano,Charles G. Mullighan,Raul Rabadan,Riccardo Dalla-Favera +16 more
TLDR
By combining next-generation sequencing and copy number analysis, it is shown that the DLBCL coding genome contains, on average, more than 30 clonally represented gene alterations per case and novel dysregulated pathways underlying its pathogenesis are identified.Abstract:
Diffuse large B-cell lymphoma (DLBCL) is the most common form of human lymphoma. Although a number of structural alterations have been associated with the pathogenesis of this malignancy, the full spectrum of genetic lesions that are present in the DLBCL genome, and therefore the identity of dysregulated cellular pathways, remains unknown. By combining next-generation sequencing and copy number analysis, we show that the DLBCL coding genome contains, on average, more than 30 clonally represented gene alterations per case. This analysis also revealed mutations in genes not previously implicated in DLBCL pathogenesis, including those regulating chromatin methylation (MLL2; 24% of samples) and immune recognition by T cells. These results provide initial data on the complexity of the DLBCL coding genome and identify novel dysregulated pathways underlying its pathogenesis.read more
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TL;DR: It is demonstrated that cancer cells containing amplifications surrounding the MCL1 and BCL2L1 anti-apoptotic genes depend on the expression of these genes for survival, and a large majority of SCNAs identified in individual cancer types are present in several cancer types.
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