Transcriptome characterization by RNA sequencing identifies a major molecular and clinical subdivision in chronic lymphocytic leukemia

• Type: Article in International Scientific Journal
• Date: 2014

Authors

Ferreira, PG (Author) Other; Jares, P (Author) Other; Rico, D (Author) Other; Gómez López, G (Author) Other; Martínez Trillos, A (Author) Other; Villamor, N (Author) Other; Ecker, S (Author) Other; González Pérez, A (Author) Other; Knowles, DG (Author) Other; Monlong, J (Author) Other; Johnson, R (Author) Other; Quesada, V (Author) Other; Djebali, S (Author) Other; Papasaikas, P (Author) Other; López Guerra, M (Author) Other; Colomer, D (Author) Other; Royo, C (Author) Other; Cazorla, M (Author) Other; Pinyol, M (Author) Other; Clot, G (Author) Other; Aymerich, M (Author) Other; Rozman, M (Author) Other; Kulis, M (Author) Other; Tamborero, D (Author) Other; Gouin, A (Author) Other; Blanc, J (Author) Other; Gut, M (Author) Other; Gut, I (Author) Other; Puente, XS (Author) Other; Pisano, DG (Author) Other; Martin Subero, JI (Author) Other; López Bigas, N (Author) Other; López Guillermo, A (Author) Other; Valencia, A (Author) Other; López Otín, C (Author) Other; Campo, E (Author) Other; Guigó, R (Author) Other

Journal

Title: Genome Research

Vol. 24

Pages: 212-226

ISSN: 1088-9051

Publisher: Cold Spring Harbor Laboratory Press

Indexing

Scopus - 160 Citations

Scientific classification

CORDIS: Natural sciences > Biological sciences > Biology > Computational biology ; Natural sciences > Biological sciences > Biology > Molecular biology

FOS: Natural sciences > Computer and information sciences ; Natural sciences > Biological sciences

Other information

Authenticus ID: P-00Q-556

DOI: 10.1101/gr.152132.112

Abstract (EN): 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. © 2014 Hansen et al.

Language: English

Type (Professor's evaluation): Scientific