A study of the epigenetics of breast cancer provides clues to mechanisms behind subtypes of the disease
Findings of study from NCMM Group Leaders, together with collaborators at Institute for Cancer Research at Oslo University Hospital, published in Nature Communications
From left: Vessela N. Kristensen, Thomas Fleischer, Xavier Tekpli and Toni Hurtado. Inserted top left: Arnoldo Frigessi. Top right: Anthony Mathelier.
Photo: Daniel Nebdal
NCMM Group Leaders, Anthony Mathelier and Toni Hurtado, together with their collaborators Thomas Fleischer and Xavier Tekpli from the Cancer Genome Variation group, led by Vessela Kristensen, at the Department of Genetics, IKF, have identified methylated regions (CpGs) that show remarkably and reproducibly conserved patterns of association to gene expression in the DNA from breast tumours in three independent breast cancer cohorts.
Aberrant DNA methylation is precisely regulated
These patterns result in two main signatures (clusters), one reflecting infiltrating immune cell signatures and another related to estrogen receptor signalling. These results indicate that, in at least some forms of cancer, aberrant DNA methylation occurs not as chaotic stochastic process, but is precisely regulated.
In fact, 80% of all CpGs that account for the associations in the estrogen receptor signalling cluster are found in enhancers - DNA segments controlling when and where genes from this pathway are expressed.
Example of successful collaboration between computational biology and clinical data
The study, published today in Nature Communications is an example of a strong collaboration between clinicians, experimental biologists, and computational biologists where the application of computational biology to clinical data derives new biological insights with potential impact for patients. Combining large scale transcriptomics with epigenomics data the scientists reveal new insights into the development and progression of breast tumours.
Help further understanding of how estrogen receptor positive breast cancers develop
These findings add significantly to our understanding of how estrogen receptor positive breast cancers develop from a luminal epithelial cell by identifying epigenetic regions specifically associated with either estrogen-receptor positive or estrogen-receptor negative breast cancer, underscoring the fact that these are biologically distinct cancers that develop differently, and thus should be treated differently.
“DNA methylation at enhancers identifies distinct breast cancer lineages” Thomas Fleischer, Xavier Tekpli, Anthony Mathelier, Shixiong Wang, Daniel Nebdal, Hari P. Dhakal, Kristine Kleivi Sahlberg, Ellen Schlichting, Oslo Breast Cancer Research Consortium (OSBREAC), Anne-Lise Børresen-Dale, Elin Borgen, Bjørn Naume, Ragnhild Eskeland, Arnoldo Frigessi, Jörg Tost, Antoni Hurtado & Vessela N. Kristensen
Nature Communications 8, 1379 (2017)
Published online: 9 November 2017, doi:10.1038/s41467-017-00510-x