Kuiper group

The growing availability of genome-wide profiling and sequencing technologies revolutionizes our understanding of cancer genomes, and provides us with opportunities to better predict risks for cancer development. Single gene mutations have been identified with a major impact on cancer risk and outcome. In the majority of cases, however, the cause of cancer onset and progression is dependent on a more complex interplay between genetic factors, which is more challenging to elucidate. To unravel this interplay of genetic factors, we apply sophisticated analyses of whole genome sequencing and transcriptomics data of both tumor samples and normal inherited DNA, with the ultimate aim to identify novel genes and mechanisms involved in an individual’s risk for cancer development and therapy response.

Renal cancer predisposition

Genetic predisposition is recognized in a substantial subset of children with renal tumors, particularly in patients with well-depicted syndromes, bilateral tumors, or a family history of cancer. For the majority of these cases, however, the genetic cause remains unknown. Furthermore, upfront recognition of enhanced genetic susceptibility in children with renal cancer is still problematic, and its prevalence is currently unknown. In collaboration with the group of prof. dr. Marry van den Heuvel-Eibrink, we investigate the frequency of known and novel genetic causes of renal cancer predisposition in children by whole exome sequencing of patients, parents and, where available, tumors, and structurally document phenotypic characteristics of these patients to optimize genetic counseling and surveillance.

Urinary bladder cancer predisposition

In collaboration with prof. dr. Bart Kiemeney and dr. Sita Vermeulen (Radboud university medical center, Nijmegen, The Netherlands) and deCODE Genetics (Reykjavik, Iceland), we currently perform a large whole genome sequencing study of familial and adolescent (<30 years of age) urinary bladder cancer patients in a patient-parent trio approach, in order to identify novel cancer predisposing genes and mechanisms. Tumor samples will be sequenced where available in order to perform an integrated germline-tumor analysis.

We focus on subclonal diversity in leukemia and its relevance for therapy response and outcome. The clonal evolution of leukemia is dynamic and strongly influenced by external factors, including therapy. Optimal treatment strategies therefore rely on the ability to constantly monitor not only the clearance of the leukemic cell population as a whole, but also those of minor subclones relative to each other. We invest in technologies that make this monitoring technically possible. I believe that most genetic factors that affect outcome, do so within a certain genomic context. Detection of cooperating events may therefore become of significant value. To be able to detect subclones in their genomic context, I expect that single cell sequencing will become increasingly important.

Technological developments in genomics research have a considerable impact on our current understanding of the genomic architecture of leukemia and will provide enormous opportunities for improved diagnosis, prognosis, and treatment. Research to test whether and how these technologies can be implemented in routine diagnostics in a cost-effective manner is extremely important for the patient. We create and test novel strategies to detect clinically relevant genomic alterations including subclonal mutations and gene fusions, which can be used to adapt the diagnostic pipeline of genetic screening of childhood ALL patients before and during treatment for optimal therapy decision making (targeted therapies).