TY  - JOUR
A1  - Ordoñez, Raquel
A1  - Kulis, Marta
A1  - Russiñol, Nuria
A1  - Chapaprieta, Vicente
A1  - Carrasco-Leon, Arantxa
A1  - García-Torre, Beatriz
A1  - Charalampopoulou, Stella
A1  - Clot, Guillem
A1  - Beekman, Renée
A1  - Meydan, Cem
A1  - Duran-Ferrer, Martí
A1  - Verdaguer-Dot, Núria
A1  - Vilarrasa-Blasi, Roser
A1  - Soler-Vila, Paula
A1  - Garate, Leire
A1  - Miranda, Estíbaliz
A1  - San José-Enériz, Edurne
A1  - Rodriguez-Madoz, Juan R.
A1  - Ezponda, Teresa
A1  - Martínez-Turrilas, Rebeca
A1  - Vilas-Zornoza, Amaia
A1  - Lara-Astiaso, David
A1  - Dupéré-Richer, Daphné
A1  - Martens, Joost H.A.
A1  - El-Omri, Halima
A1  - Taha, Ruba Y.
A1  - Calasanz, Maria J.
A1  - Paiva, Bruno
A1  - San Miguel, Jesus
A1  - Flicek, Paul
A1  - Gut, Ivo
A1  - Melnick, Ari
A1  - Mitsiades, Constantine S.
A1  - Licht, Jonathan D.
A1  - Campo, Elias
A1  - Stunnenberg, Hendrik G.
A1  - Agirre, Xabier
A1  - Prosper, Felipe
A1  - Martin-Subero, Jose I.
T1  - Chromatin activation as a unifying principle underlying pathogenic mechanisms in multiple myeloma
Y1  - 2020/09/01 
JF  - Genome Research 
JO  - Genome Research 
SP  - 1217 
EP  - 1227 
DO  - 10.1101/gr.265520.120 
VL  - 30 
IS  - 9 
UR  - http://genome.cshlp.org/content/30/9/1217.abstract 
N2  - Multiple myeloma (MM) is a plasma cell neoplasm associated with a broad variety of genetic lesions. In spite of this genetic heterogeneity, MMs share a characteristic malignant phenotype whose underlying molecular basis remains poorly characterized. In the present study, we examined plasma cells from MM using a multi-epigenomics approach and demonstrated that, when compared to normal B cells, malignant plasma cells showed an extensive activation of regulatory elements, in part affecting coregulated adjacent genes. Among target genes up-regulated by this process, we found members of the NOTCH, NF-kB, MTOR signaling, and TP53 signaling pathways. Other activated genes included sets involved in osteoblast differentiation and response to oxidative stress, all of which have been shown to be associated with the MM phenotype and clinical behavior. We functionally characterized MM-specific active distant enhancers controlling the expression of thioredoxin (TXN), a major regulator of cellular redox status and, in addition, identified PRDM5 as a novel essential gene for MM. Collectively, our data indicate that aberrant chromatin activation is a unifying feature underlying the malignant plasma cell phenotype. 
ER  -