title: Analysis of the coding genome of diffuse large B-cell lymphoma.
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.
authors.affiliation: Institute for Cancer Genetics, Columbia University, New York, New York, USA. lp171@columbia.edu
authors.forename: Laura
authors.initials: L
authors.lastname: Pasqualucci
authors.forename: Vladimir
authors.initials: V
authors.lastname: Trifonov
authors.forename: Giulia
authors.initials: G
authors.lastname: Fabbri
authors.forename: Jing
authors.initials: J
authors.lastname: Ma
authors.forename: Davide
authors.initials: D
authors.lastname: Rossi
authors.forename: Annalisa
authors.initials: A
authors.lastname: Chiarenza
authors.forename: Victoria A
authors.initials: VA
authors.lastname: Wells
authors.forename: Adina
authors.initials: A
authors.lastname: Grunn
authors.forename: Monica
authors.initials: M
authors.lastname: Messina
authors.forename: Oliver
authors.initials: O
authors.lastname: Elliot
authors.forename: Joseph
authors.initials: J
authors.lastname: Chan
authors.forename: Govind
authors.initials: G
authors.lastname: Bhagat
authors.forename: Amy
authors.initials: A
authors.lastname: Chadburn
authors.forename: Gianluca
authors.initials: G
authors.lastname: Gaidano
authors.forename: Charles G
authors.initials: CG
authors.lastname: Mullighan
authors.forename: Raul
authors.initials: R
authors.lastname: Rabadan
authors.forename: Riccardo
authors.initials: R
authors.lastname: Dalla-Favera
mesh_terms: D002843:Chromatin / Q000378:metabolism; D004252:DNA Mutational Analysis; D004171:Diploidy; D018628:Gene Dosage; D015973:Gene Expression Regulation, Leukemic; D015894:Genome, Human; D018858:Germinal Center / Q000276:immunology; D006801:Humans; D016403:Lymphoma, Large B-Cell, Diffuse / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D008745:Methylation; D009364:Neoplasm Recurrence, Local / Q000235:genetics / Q000276:immunology / Q000473:pathology; D017354:Point Mutation; D020641:Polymorphism, Single Nucleotide; D013601:T-Lymphocytes / Q000276:immunology
chemical_list: D002843:Chromatin