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Kemmeren group

The Kemmeren group exploits cancer genomics data through a combination of bioinformatics and systems biology approaches with the goal to improve our understanding of childhood cancer initiation and progress as well as improve patient care for children with cancer. Examples include driving bioinformatics research for precision oncology and diagnostics, improving structural variation detection and investigating biological mechanisms of genetic interactions in childhood cancer. We have developed a unique combination of expertise in bioinformatics, functional genomics and molecular-genetic interactions. While our focus is on computational aspects, we collaborate intensively with (pediatric) tumor biology groups, thus enabling a truly multidisciplinary approach.

Group leader: Dr. Patrick Kemmeren
Telefoon +31 88 972 7272
Mechanisms of genetic interactions in pediatric cancer

Cancers arise and progress through the acquirement of combinations of mutations. Genetic interactions are specific combinations of mutations that have unpredictable phenotypic consequences. Thorough understanding of genetic interactions, their underlying mechanisms and relation to pediatric cancer is crucial for deciphering cancer predisposition, onset and progression as well as for developing precision medicine approaches. Two genetic interaction types are of particular importance for cancer. Detailed understanding of cooperative interactions will aid in elucidating general principles governing cancer onset and progression. Understanding mutually exclusive interactions is pivotal for developing more effective cancer drugs. We investigate the role of genetic interactions and their contribution to different pediatric cancers. We focus on cooperative and mutually exclusive interactions between genes, pathways and processes altered in pediatric cancers as exhibited in cancer genomes of patients. We also include common variants associated with pediatric cancer and propose mechanistic models for cooperative and mutually exclusive interactions using a combination of bioinformatics, systems biology and wet-lab follow up verification and validation experiments.

"Bioinformatics is essential for transforming genomic data into knowledge within pediatric cancer research." Dr. Patrick Kemmeren - Group leader
Contribution of structural variation in pediatric cancer

Structural variants (SVs) and in particular gene-fusions are important for prognosis and diagnosis of pediatric cancer, can drive tumorigenesis and serve as therapeutic targets. While targeted assays provide a fast and cost-effective way to detect gene-fusions, they are limited to known breakpoints or partner genes. Instead, we leverage RNA-seq and whole genome sequencing (WGS) to detect clinically relevant gene fusions and other types of SVs and copy number alterations (CNAs). By combining RNA-seq and WGS, we investigate the contribution of SVs in pediatric cancer and study their underlying mechanisms, effect on cancer biology and potential use for diagnosis and treatment stratification. Combined analysis of SVs, CNAs and expression data is likely to aid in interpretation and infer potential effects. Through identification of potentially pathogenic SVs, we intend to elucidate disease mechanisms and identify novel therapeutic targets in patients lacking known driver mutations.


Classification of pediatric tumor (sub)types

Pediatric cancers types are usually diagnosed based on histopathological features. These cancer types however frequently display clinically heterogenous behavior. Improved classification of pediatric cancer subtypes can lead to targeted therapeutic strategies and ultimately lead to an increase in survival. For diagnostic purposes, DNA methylation profiling in addition to whole exome sequencing and RNA sequencing is used for brain and solid tumors. Together with the diagnostics laboratory (head Bas Tops), we develop DNA methylation and RNA-seq analyses pipelines for both diagnostic and research purposes to discover and predict distinct tumor subtypes for improved cancer treatment.

Big Data Core facility

The availability of a plethora of genomics technologies have drastically changed many life sciences, including cancer research, into a data-driven research field. Uniform and systematic access to these data and the underlying patient samples is essential for modern pediatric oncology research. Institute-wide coordination concerning data stewardship, data infrastructures and computational infrastructures is pivotal for making optimal use of data for pediatric cancer research and care. The Big Data Core facility consolidates these activities and performs bioinformatics analyses for the Máxima biobank and diagnostic laboratory. For more information, see the Big Data Core facility webpage.

Bioinformatics expertise core

The Bioinformatics expertise core consists of several bioinformaticians, computational scientists, bioinformatic analysts and data scientists that are part of the different research groups located within the Princess Máxima Center. Our aims are to create an expertise group of people all working in bioinformatics or systems biology, using a common set of rules and guidelines to facilitate code sharing and reuse as well as coordinating the core bioinformatics infrastructure needs for our research activities. This expertise core is coordinated by the Kemmeren group and includes bioinformaticians and computational biologists from many other research groups.




Kemmeren group