Proteogenomics and Hi-C reveal transcriptional dysregulation in high hyperdiploid childhood acute lymphoblastic leukemia

Minjun Yang; Mattias Vesterlund; Ioannis Siavelis; Larissa H. Moura-Castro; Anders Castor; Thoas Fioretos; Rozbeh Jafari; Henrik Lilljebjörn; Duncan T. Odom; Linda Olsson; Naveen Ravi; Eleanor L. Woodward; Louise Harewood; Janne Lehtiö; Kajsa Paulsson

doi:10.1038/s41467-019-09469-3

Proteogenomics and Hi-C reveal transcriptional dysregulation in high hyperdiploid childhood acute lymphoblastic leukemia

Minjun Yang, Mattias Vesterlund, Ioannis Siavelis, Larissa H. Moura-Castro, Anders Castor, Thoas Fioretos, Rozbeh Jafari, Henrik Lilljebjörn, Duncan T. Odom, Linda Olsson, Naveen Ravi, Eleanor L. Woodward, Louise Harewood, Janne Lehtiö, Kajsa Paulsson

Research output: Contribution to journal › Article › peer-review

Abstract

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.

Original language	English
Article number	1519
Journal	Nature Communications
Volume	10
Issue number	1
DOIs	https://doi.org/10.1038/s41467-019-09469-3
Publication status	Published - 2019 Apr 3

Subject classification (UKÄ)

Medical Genetics and Genomics (including Gene Therapy)
Cancer and Oncology
Pediatrics

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This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1038/s41467-019-09469-3

1 Doctoral Thesis (compilation)

Unwinding the layers of high hyperdiploid childhood acute lymphoblastic leukemia
Moura-Castro, L. H., 2024, Lund: Lund University, Faculty of Medicine. 81 p.
Research output: Thesis › Doctoral Thesis (compilation)

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Yang, M., Vesterlund, M., Siavelis, I., Moura-Castro, L. H., Castor, A., Fioretos, T., Jafari, R., Lilljebjörn, H., Odom, D. T., Olsson, L., Ravi, N., Woodward, E. L., Harewood, L., Lehtiö, J., & Paulsson, K. (2019). Proteogenomics and Hi-C reveal transcriptional dysregulation in high hyperdiploid childhood acute lymphoblastic leukemia. Nature Communications, 10(1), Article 1519. https://doi.org/10.1038/s41467-019-09469-3

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title = "Proteogenomics and Hi-C reveal transcriptional dysregulation in high hyperdiploid childhood acute lymphoblastic leukemia",

abstract = "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.",

author = "Minjun Yang and Mattias Vesterlund and Ioannis Siavelis and Moura-Castro, {Larissa H.} and Anders Castor and Thoas Fioretos and Rozbeh Jafari and Henrik Lilljebj{\"o}rn and Odom, {Duncan T.} and Linda Olsson and Naveen Ravi and Woodward, {Eleanor L.} and Louise Harewood and Janne Lehti{\"o} and Kajsa Paulsson",

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Yang, M, Vesterlund, M, Siavelis, I, Moura-Castro, LH , Castor, A , Fioretos, T, Jafari, R, Lilljebjörn, H, Odom, DT, Olsson, L, Ravi, N, Woodward, EL, Harewood, L, Lehtiö, J & Paulsson, K 2019, 'Proteogenomics and Hi-C reveal transcriptional dysregulation in high hyperdiploid childhood acute lymphoblastic leukemia', Nature Communications, vol. 10, no. 1, 1519. https://doi.org/10.1038/s41467-019-09469-3

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T1 - Proteogenomics and Hi-C reveal transcriptional dysregulation in high hyperdiploid childhood acute lymphoblastic leukemia

AU - Yang, Minjun

AU - Vesterlund, Mattias

AU - Siavelis, Ioannis

AU - Moura-Castro, Larissa H.

AU - Castor, Anders

AU - Fioretos, Thoas

AU - Jafari, Rozbeh

AU - Lilljebjörn, Henrik

AU - Odom, Duncan T.

AU - Olsson, Linda

AU - Ravi, Naveen

AU - Woodward, Eleanor L.

AU - Harewood, Louise

AU - Lehtiö, Janne

AU - Paulsson, Kajsa

PY - 2019/4/3

Y1 - 2019/4/3

N2 - 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.

AB - 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.

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DO - 10.1038/s41467-019-09469-3

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AN - SCOPUS:85063941879

SN - 2041-1723

VL - 10

JO - Nature Communications

JF - Nature Communications

IS - 1

M1 - 1519

ER -

Proteogenomics and Hi-C reveal transcriptional dysregulation in high hyperdiploid childhood acute lymphoblastic leukemia

Abstract

Subject classification (UKÄ)

UN SDGs

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Research output

Unwinding the layers of high hyperdiploid childhood acute lymphoblastic leukemia

Cite this