The mutational landscape in pediatric acute lymphoblastic leukemia deciphered by whole genome sequencing

Published: 2014-11-10

Researchers at SciLifeLab have published a detailed study of the genomes of pediatric acute lymphoblastic leukemia (ALL) patients, together with pediatric oncologists from the university hospitals in Göteborg, Stockholm, Umeå and Uppsala.


The complete leukemic genomes of bone marrow samples from four ALL patients were characterized by whole genome sequencing. Genomic regions with somatic ALL mutations were further sequenced in 168 additional ALL patients to detect recurrent mutations. This analysis identified KMT2D and KIF1B as novel putative ALL driver genes. Moreover, a non-coding mutation that coincided with over-expression of the growth factor MDK was detected. Sequencing was performed at the laboratories of the National Genomics Infrastructure, SNP&SEQ Platform.

– The results from the study suggest that regulatory genetic variants are more important for cancer development than recognized to date. Our results emphasize the benefits of whole genome sequencing, particularly in ALL which is a genetically heterogeneous disease, said Dr Eva Berglund who led the bioinformatic analyses in the project.

The project received support from the Bioinformatics Long-term Support (WABI), which speeded up the analysis, according to PhD student Mårten Lindqvist, at the Molecular Medicine research group at Uppsala University, who performed much of the analyses in this project.

The study is one of the first published studies in which whole human genomes, that comprise 3 billion base pairs of DNA, have been sequenced and the data has been fully analyzed within Sweden. It took three years to complete the study, mainly because new bioinformatic tools had to be established to analyze the large data sets.

During 2015 SciLifeLab will begin to offer whole genome sequencing on a much larger scale to Swedish researchers using newly purchased HiSeqX machines to NGI in Stockholm and Uppsala, funded by the Knut and Alice Wallenberg Foundation.

– We are now entering a new era of human disease genomics. With the new sequencing capacity, NGI can sequence 10,000 whole genomes per year. An automated bioinformatics pipeline for handling and primary analysis of the large data sets to be produced will soon be in place. We are confident that the work that we are now starting up will have a great impact on research and diagnostics of human diseases, said professor Ann-Christine Syvänen, who heads the SNP&SEQ Platform.

Read the article at Wiley Online Library