The 3-dimensional breast cancer genome
Can the spatial distribution of mutations and SNPs in the nucleus constitute a new level of breast cancer sub-classification? The 3-dimensional breast cancer genome project is developing tools to tackle this question.
Chrom3D in a user-friendly environment; here, our prototype for iPhones and Androids. © CollasLab.
With nearly 2 million new cases diagnosed yearly, breast cancer is the second most lethal cancer among women worldwide. Cancer DNA variation seems to be related to the underlying 3D conformation of the genome. We reason that the spatial distribution of breast cancer mutations in the cell nucleus may be used as level of classification of breast tumor types and patients. We are developing tools to map the 3D distribution of breast cancer mutations in the nucleus and assess whether the 3D pattern of breast cancer SNPs constitutes a new level of breast cancer type sub-classification.
About the project
We hypothesize that 3D genome organization affects the susceptibility of genomic regions to mutagenesis and constitutes a new level of assessment of tumorigenicity. We are developing tools to map the 3D distribution of breast cancer mutations in the nucleus and assess whether the 3D pattern of breast cancer SNPs constitutes a new level of breast cancer type sub-classification. We also examine nuclear envelope and chromatin architectural changes in cellular models of breast cancer progression.
- Computational methods for large-scale 3D modeling of chromatin
- 3D mapping of breast cancer DNA variation in the nucleus
- Relationship between the nuclear lamina, genome architecture and progression to metastasis
Outcomes / Recent findings
- Genomic characterization of cliques of topological domains (TADs) in cancer cell lines
- Physical properties of chromatin as a polymer which affect dynamics and patterns of interactions with the nuclear lamina (Brunet et al. 2021 Nucleus 12, 6-20)
- Long-range associations between TADs form cliques that shape the dynamic 3D genome (Paulsen et al 2019 Nat. Genet 5, 835-843)
- UV-induced DNA lesions are enriched at the nuclear periphery (Garcia-Nieto et al 2017 EMBO J 36, 2829-2843)
- Chrom3D: a computational platform for 3D genome modeling (Paulsen et al 2018 Nat Prot 13, 1137-1152; Paulsen et al 2017 Genome Biol 18:21)
- Jonas Paulsen, Section for Genetics and Evolutionary Biology, Institute of Biosciences, University of Oslo, Oslo, Norway
- Vessela Kristensen, Cancer Genome Variation Group, Oslo University Hospital, Oslo, Norway
- David Tremethick, Department of Genome Science, The John Curtin Scholl of Medical Research, The Australian National University, Canberra, Australia