M Yang, M Vesterlund, I Siavelis, LH Moura-Castro, A Castor, T Fioretos, R Jafari, H Lilljebjörn, DT Odom, L Olsson, N Ravi, EL Woodward, L Harewood, J Lehtiö, K Paulsson
Journal name: 
Nat Commun
Citation info: 
Hyperdiploidy, i.e. gain of whole chromosomes, is one of the most common genetic features of childhood acute lymphoblastic leukemia (ALL), but its pathogenetic impact is poorly understood. Here, we report a proteogenomic analysis on matched datasets from genomic profiling, RNA-sequencing, and mass spectrometry-based analysis of >8,000 genes and proteins as well as Hi-C of primary patient samples from hyperdiploid and ETV6/RUNX1-positive pediatric ALL. We show that CTCF and cohesin, which are master regulators of chromatin architecture, display low expression in hyperdiploid ALL. In line with this, a general genome-wide dysregulation of gene expression in relation to topologically associating domain (TAD) borders were seen in the hyperdiploid group. Furthermore, Hi-C of a limited number of hyperdiploid childhood ALL cases revealed that 2/4 cases displayed a clear loss of TAD boundary strength and 3/4 showed reduced insulation at TAD borders, with putative leukemogenic effects.
Research group: 
Odom Group
E-pub date: 
31 Mar 2019
Users with this publication listed: 
Duncan Odom
Louise Harewood