Please use this identifier to cite or link to this item: http://hdl.handle.net/2445/108603
Title: Transcriptome characterization by RNA sequencing identifies a major molecular and clinical subdivision in chronic lymphocytic leukemia
Author: Ferreira, Pedro G.
Jares Gerboles, Pedro
Rico, Daniel
Gómez-López, Gonzalo
Martínez-Trillos, Alejandra
Villamor, Neus
Ecker, Simone
González-Pérez, Abel
Knowles, David G.
Monlong, Jean
Johnson, Rory
Quesada, Victor
Djebali, Sarah
Papasaikas, Panagiotis
López-Guerra, Mónica
Colomer Pujol, Dolors
Royo, Cristina
Cazorla, Maite
Pinyol, Magda
Clot, Guillem
Aymerich, Marta
Rozman, María
Kulis, Marta
Tamborero, David
Gouin, Anaïs
Blanc, Julie
Gut, Marta
Gut, Ivo
Puente, Xose S.
Pisano, David G.
Martín-Subero, José Ignacio
López-Bigas, Núria
López Guillermo, Armando
Valencia, Alfonso
López-Otín, Carlos
Campo Güerri, Elias
Guigó Serra, Roderic
Keywords: Leucèmia limfocítica crònica
Cèl·lules B
Expressió gènica
Genètica molecular
Chronic lymphocytic leukemia
B cells
Gene expression
Molecular genetics
Issue Date: 21-Nov-2013
Publisher: Cold Spring Harbor Laboratory Press
Abstract: Chronic lymphocytic leukemia (CLL) has heterogeneous clinical and biological behavior. Whole-genome and -exome sequencing has contributed to the characterization of the mutational spectrum of the disease, but the underlying transcriptional profile is still poorly understood. We have performed deep RNA sequencing in different subpopulations of normal B-lymphocytes and CLL cells from a cohort of 98 patients, and characterized the CLL transcriptional landscape with unprecedented resolution. We detected thousands of transcriptional elements differentially expressed between the CLL and normal B cells, including protein-coding genes, noncoding RNAs, and pseudogenes. Transposable elements are globally derepressed in CLL cells. In addition, two thousand genes-most of which are not differentially expressed-exhibit CLL-specific splicing patterns. Genes involved in metabolic pathways showed higher expression in CLL, while genes related to spliceosome, proteasome, and ribosome were among the most down-regulated in CLL. Clustering of the CLL samples according to RNA-seq derived gene expression levels unveiled two robust molecular subgroups, C1 and C2. C1/C2 subgroups and the mutational status of the immunoglobulin heavy variable (IGHV) region were the only independent variables in predicting time to treatment in a multivariate analysis with main clinico-biological features. This subdivision was validated in an independent cohort of patients monitored through DNA microarrays. Further analysis shows that B-cell receptor (BCR) activation in the microenvironment of the lymph node may be at the origin of the C1/C2 differences.
Note: Reproducció del document publicat a: https://doi.org/10.1101/gr.152132
It is part of: Genome Research, 2013, vol. 24, num. 2, p. 212-226
Related resource: https://doi.org/10.1101/gr.152132
URI: http://hdl.handle.net/2445/108603
ISSN: 1088-9051
Appears in Collections:Articles publicats en revistes (IDIBAPS: Institut d'investigacions Biomèdiques August Pi i Sunyer)
Articles publicats en revistes (Fonaments Clínics)

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