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Arthur Boffelli Castro - Institutionen för experimentell medicinsk vetenskap
Title: Roads to increased heritable variation in animal and cancer species
Main supervisor: Emma Hammarlund
Reviewers: Helena Persson, Kasper Karlsson
Abstract
Background
A subset of cancer cells can adopt an increased genomic content (IGC) state in response to stressors like chemotherapy, radiation, and hypoxia. These cells increase their genomic content through mechanisms such as endocycling, resulting in mononucleated giant cells. Initially thought to face mitotic failure or apoptosis, recent studies highlight their critical role in cancer progression and metastasis.
Cells with IGC exhibit enhanced motility, environmental adaptability, and invasion potential, making them crucial for understanding recurrence and metastasis. They can depolyploidize, resuming mitosis and producing progeny. Progeny typically emerge after 2–8 weeks of dormancy and may display altered phenotypes or resistance traits, potentially influencing tumor evolution.
Further research is needed to understand the long-term effects of IGC-derived progeny and to develop methods for distinguishing them from parental cells in tissues, as their role in cancer progression remains underexplored.
Research questions
The purpose of my projects is to explore the relationship between polyploidy and heritable variability. Does a state where cancer cells employ a stress response by endocycling result in increased resistance mechanisms through genomic or epigenomic changes, and what are these changes?
We aim on understanding the changes in the progeny after undergoing the polyploid state, and their relationship with cancer recurrence
Preliminary results
The presence of cells with IGC in primary tumour samples show potential as a prognostic feature for reduced recurrence-free survival in patients classified as NHG 2.
In vitro, we observed that the progeny is genomically similar to the parental cells, however they show differentially expressed genes and changes in the chromatin accessibility.
Significance
The NHG 2 is not as clinically informative as the other two NHGs, since it has an intermediate risk that can vary into low or high. The presence of cells with IGC could serve as a valuable feature for improving the stratification of the controversial NHG 2 classification, resulting in a better treatment for patients. In addition, understanding the changes in the progeny after undergoing the polyploid state, and their relationship with cancer recurrence can contribute to cancer treatment and act as a model for animal evolution.
Published studies
No published studies.
Om evenemanget
Plats:
BMC:I1345 Sölvegatan 19, 223 62 Lund
Kontakt:
arthur [dot] boffelli_castro [at] med [dot] lu [dot] se