Kemmeren group

PI: Dr. Patrick Kemmeren

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. In particular, 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 - PI

Biobanking and genomics BIG data for diagnostics and research

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. For diagnostic purposes whole exome sequencing (WES) and RNA sequencing will be performed as standard of care. For research purposes, additional whole genome sequencing (WGS) and DNA methylation profiling will be performed. In both scenarios, primary patient material and research derived materials will be stored in a biobank and characterized at the molecular level through WES, WGS, RNA-seq and DNA methylation analyses. Together with the molecular diagnostics lab and Holstege lab , we are developing an integrated platform for sample tracking, data management, data integration and data analytics of these genomics BIG data. 

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 tumors. The aim is to perform DNA methylation profiling for solid tumors and potentially hematological tumors in the near future as well. Together with the molecular diagnostics lab and Holstege lab, we are currently developing DNA methylation analyses pipelines for both diagnostic and research purposes to discover and predict distinct tumor subtypes for improved cancer treatment.

Bioinformatics expertise core

The Bioinformatics expertise core consists of a number of 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. These efforts are coordinated by the Kemmeren group and includes bioinformaticians and computational biologists from the Holstege, Kuiper, den Boer, Meijerink and van Boxtel groups.