Yesterday Jurrian de Kanter, PhD student of the Van Boxtel group, defended his thesis entitled: "Finding the hidden patterns: single-cell comics to reduce late effects" cum laude. We want to congratulate him with this great achievement!
Read More"To beat cancer, we need to know how it starts."
Identifying the rate limiting steps of cancer initiation in human tissues is challenging as many factors can play a role. The mutations in the genomes of cells can serve as an archive of their life history. We aim to decode these archives in order to pinpoint the initiation of cancer and identify causal processes in human tissues. To study the etiology of cancer, we have 3 research themes in our lab.
Learn MoreOrgan-specific cancer incidence varies significantly throughout the human body, which cannot be solely explained by different exposures to mutagenic environmental. Adult stem cells are likely the cellular targets for accumulation of pre-cancerous successive oncogenic hits, which eventually can give rise to tumor development, owing to their life-long capacity to propagate mutations to both self-renewing progeny and downstream progenitors. We aim to identify and study the mutational processes that are active in adult stem cells of various organs and precede oncogenic transformation.
Learn MoreDNA is the largest biomolecule in the cells, which unlike other biomolecules is irreplaceable. The processes causing mutations leave characteristic patterns in the DNA, which can serve as a functional readout of mutagenic and/or DNA repair activity. In addition, phylogenetic relationships between different cells of the same individual can be exploited measure clonal dynamics within tissues. We aim to identify and study the mechanisms underlying characteristic mutation patterns in cancers as well as use mutations to retrospectively trace the cellular origin of cancer.
Learn MoreMost chemotherapeutic drugs act by fatally damaging the DNA or blocking the replication thereof. However, noncancerous cells are also damaged by treatment, which can result in the accumulation of DNA mutations in normal tissues with potentially adverse effects later in life, such as novel malignancies. Our goal is to study the mutational effects of cancer treatment in normal tissues of children in order to develop novel treatment strategies aimed at minimizing or preventing adverse late effects.
Learn MoreYesterday Jurrian de Kanter, PhD student of the Van Boxtel group, defended his thesis entitled: "Finding the hidden patterns: single-cell comics to reduce late effects" cum laude. We want to congratulate him with this great achievement!
Read MoreCo-culture of intestinal organoids with a colibactin-producing pks+ E. coli strain (EcC) revealed mutational signatures also found in colorectal cancer (CRC).
Read MoreRuben, has been awarded an NWO Vici grant. With the prestigious grant, Van Boxtel can further expand his research line into the late effects of childhood cancer and how these are reflected at a molecular cell level.
Read MoreJust before Christmas on December 21st, our PhD student Flavia Peci defended her thesis "Genomic Safety of Transplantation; characterising the Mutational Consequences of Treatment in Hematopoietic Stem Cells".
Read MoreTuesday our PhD student Eline Bertrums defended her thesis defence entitled: "The Clonal Dynamics underlying the genesis and regression of myeloid disorders", with cum laude.
Read MoreIn our lab we developed the computational PTA Analysis Toolbox (PTATO) that can effectively filter artifacts from PTA-based WGS data, enabling accurate analyses of somatic mutations in single cells at nucleotide resolution.
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In this study, Rosendahl Huber et al. show the mutagenic properties of pks E. coli strains, including probiotic E. coli Nissle 1917, using the extended target sequence context of colibactin and with a machine-learning model. These approaches allow for better distinguishing of colibactin-associated colorectal cancer cases, which are younger and are enriched for APC mutations matching the colibactin motif.
Read MoreDetection of somatic mutations in single cells is challenging, in part because whole-genome amplification causes many artificial mutations. Middelkamp et al. developed the computational PTA Analysis Toolbox (PTATO) that can effectively filter artifacts from PTA-based WGS data, enabling accurate analyses of somatic mutations in single cells at nucleotide resolution.
Read MoreChemotherapy increases the mutation burden of normal blood cells in cancer survivors. Only few drugs damage the DNA directly, while in most patients, chemotherapy-induced mutations are caused by processes similar to those present during normal aging. Cancer Discovery 2022
Read MoreAntiviral treatment with ganciclovir causes a unique mutational signature in stem cells of human transplant recipients. This signature was also found in therapy-related cancers and can cause cancer driver mutations. Cell Stem Cell 2021
Read MoreIn some children with acute myeloid leukemia, cancer cells have the same amount of DNA changes as healthy blood stem cells. Here, we show that these children have a poorer chance of survival compared to children whose leukemia has an above-average number of DNA changes. This study offers insight into how this form of blood cancer can develop in children. In the future, these findings may help identify which patients have a high-risk form of the disease. Blood Cancer Discovery 2021
Read MoreOur study describes a distinct mutational signature in colorectal cancer and implies that the underlying mutational process results directly from past exposure to bacteria carrying the colibactin-producing pks pathogenicity island. Nature 2020
Read MoreMutation accumulation during life can contribute to hematopoietic dysfunction; however, the underlying dynamics are unknown. Using mutations found in in acute myeloid leukemia, we construct a developmental lineage tree of human hematopoiesis, revealing a polyclonal architecture and providing evidence that developmental clones exhibit multipotency. Cell Reports 2018
Read MoreHere we determine genome-wide mutation patterns in human adult stem cells of the small intestine, colon and liver of human donors with ages ranging from 3 to 87 years by sequencing clonal organoid cultures derived from primary multipotent cells. Our results show that mutations accumulate steadily over time in all of the assessed tissue types, at a rate of approximately 40 novel mutations per year, despite the large variation in cancer incidence among these tissues. Nature 2016
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