CSCI International Seminar - Dr. Jacco van Rheenen

Prof. Jacco van Rheenen

Deputy Director of the Netherlands Cancer Institute (NKI), Principal Investigator at the NKI and Oncode Institute, and Professor at the UMC Utrecht

Title: "Puberty as a Superspreader of Mutations Elevating Tumor Long-term Risk in Breast Tissue"

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Abstract:

Aging increases the mutational burden of breast tissues, yet even in healthy young adults numerous cells with mutations in breast cancer-associated genes are found. Remodelling of the adult ductal network through the hormonal cycle drives the propagation of these mutant cells, increasing the risk of tumorigenesis. Pubertal morphogenesis, however, represents the most extensive remodelling phase, raising the question how this developmental window influences mutation propagation and cancer risk. 

Here, we developed computational modelling, imaging, and sequencing techniques to track over time the propagation of clones with somatic mutations during puberty in human and mouse tissues. We show that pubertal branching morphogenesis serves as a propagation burst for somatic mutations, widely dispersing them across the ductal tree in a unique skip pattern. This creates regions of heightened vulnerability for morphological transformation throughout the ductal network. 

Supporting this, three-dimensional imaging of mammary ducts in BRCA2 mutation carriers and ductal carcinoma in-situ (DCIS) resections identified small lesions co-occurring in form of the pubertal skip pattern involving large areas of the ductal network. These findings highlight pubertal mammary gland development as a clonal propagation burst of somatic mutations, emphasizing the need to consider early-life events in breast cancer prevention and research.
 

About Prof. van Rheenen:

In 2008, Prof. van Rheenen was appointed as group leader at the Hubrecht Institute, where he utilizes his imaging techniques to visualize processes that are required for the metastasis of tumour cells in living animals. In July 2014 he was appointed full professor in Intravital Microscopy at the University Medical Center Utrecht. In October 2017 he became senior group leader at the Netherlands Cancer Institute (NKI) and the Oncode Institute. In 2009, he was awarded a VIDI, and in 2022 a VICI award from Netherlands Organization for Scientific Research. In 2013, he received the Stem Cells Young Investigator Award. In 2015, he was awarded an ERC consolidator grant, in 2017 the Dr. Josef Steiner Cancer Research Foundation Award, and in 2019 the Ammodo Science Award. Jacco is EMBO member and deputy director of the NKI.