Proteogenomics and Hi-C reveal transcriptional dysregulation in high hyperdiploid childhood acute lymphoblastic leukemia.
Adolescent
Aneuploidy
CCCTC-Binding Factor
/ genetics
Cell Cycle Proteins
/ genetics
Child
Child, Preschool
Chromatin
/ genetics
Chromosomal Proteins, Non-Histone
/ genetics
Chromosome Aberrations
Core Binding Factor Alpha 2 Subunit
/ genetics
Female
Gene Dosage
Gene Expression Profiling
Gene Expression Regulation, Leukemic
Genome, Human
Genome-Wide Association Study
Humans
Infant
Infant, Newborn
Male
Precursor Cell Lymphoblastic Leukemia-Lymphoma
/ genetics
Proteogenomics
/ methods
Proteome
/ genetics
Proto-Oncogene Proteins c-ets
/ genetics
Repressor Proteins
/ genetics
Sequence Analysis, RNA
Transcription, Genetic
Cohesins
ETS Translocation Variant 6 Protein
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
03 04 2019
03 04 2019
Historique:
received:
18
07
2018
accepted:
11
03
2019
entrez:
5
4
2019
pubmed:
5
4
2019
medline:
30
4
2019
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 30944321
doi: 10.1038/s41467-019-09469-3
pii: 10.1038/s41467-019-09469-3
pmc: PMC6447538
doi:
Substances chimiques
CCCTC-Binding Factor
0
CTCF protein, human
0
Cell Cycle Proteins
0
Chromatin
0
Chromosomal Proteins, Non-Histone
0
Core Binding Factor Alpha 2 Subunit
0
Proteome
0
Proto-Oncogene Proteins c-ets
0
RUNX1 protein, human
0
Repressor Proteins
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
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