Aneuploidy in Cancer

Gains and losses of whole chromosomes, termed aneuploidy, is seen in at least half of all tumors. How it affects tumorigenesis is still poorly understood. We use hyperdiploid (51-67 chromosomes) pediatric acute lymphoblastic leukemia (ALL) as a model to study aneuploidy, focusing on:

1. How does the cell become aneuploid? We use large-scale sequencing and array-based analyses of bulk and single cells as well as experimental systems to understand whether aneuploidy is always associated with chromosomal instability (CIN) and to delineate the pathways by which aneuploidy arise.
2. How do gain or loss of chromosomes drive cancer? We study how aneuploidy affects the transcriptome and proteome as well as the role of chromatin architecture in in the context of aneuploidy, using NGS-based methods as well as cytogenetic analyses of chromosomes.

By addressing these questions, we will get novel insight into how aneuploidy affect tumor cells that may be used to develop novel therapies and improve treatment stratification.

Selected publications

Moura-Castro LH, Peña-Martínes P, Castor A, Galeev R, Larsson J, Järås M, Yang M, Paulsson K. Sister chromatid cohesion defects are associated with chromosomal copy number heterogeneity in high hyperdiploid childhood acute lymphoblastic leukemia. Genes Chromosomes Cancer 2021:60(6):410-417 (link: https://onlinelibrary.wiley.com/doi/10.1002/gcc.22933).

Yang M, Safavi S, Woodward EL, Duployez N, Olsson-Arvidsson L, Ungerbäck J, Sigvardsson M, Zaliova M, Zuna J, Fioretos T, Johansson B, Nord KH, Paulsson K. 13q12.2 deletions in acute lymphoblastic leukemia lead to upregulation of FLT3 through enhancer hijackin. Blood 2020;136:946-956.

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. Proteogenomics and Hi-C reveal transcriptional dysregulation in high hyperdiploid childhood acute lymphoblastic leukemia. Nat Commun 2019;10:1519. 

Ravi N, Yang M, Gretarsson S, Jansson C, Mylona N, Sydow SR, Woodward EL, Ekblad L, Wennerberg J, Paulsson K. Identification of targetable lesions in anaplastic thyroid cancer by genome profiling. Cancers 2019;11:402.

Paulsson K, Lilljebjörn H, Biloglav A, Olsson L, Rissler M, Castor A, Barbany G, Fogelstrand L, Nordgren A, Sjögren H, Fioretos T, Johansson B. The genomic landscape of high hyperdiploid childhood acute lymphoblastic leukemia. Nat Genet 2015;47:672-676. 
 

Funding

Our research is funded by the Swedish Research Council, the Swedish Cancer Fund, the Swedish Childhood Cancer Foundation, the Crafoord Foundation, Governmental Funding of Clinical Research within National Health Service (ALF) and BioCARE.