Marc Williams

Fluctuating DNA methylation tracks cancer evolution at clinical scale - Nature Cancer evolutionary dynamics are quantitatively inferred using a method, EVOFLUx, applied to fluctuating DNA methylation.

Studying cancer evolution needs multi-region or single cell seq for phylogenetics, right? Amazingly (I think!) we found single-sample bulk methylation suffices, via analysis of "fluctuating methylation". In @nature.com today led by brilliant @calumgabbutt.bsky.social www.nature.com/articles/s41...

congrats Trevor and @calumgabbutt.bsky.social, great to see this out. Still kind of amazed by Figure 5!

Interestingly we didn't see much evidence of any intermediate genomes between these two states

For the highly aneuploid cells that look like cancer genomes, I would guess they are some kind of pre-cancer clone and there may have been some kind of pre-malignant lesion that was too small for us to see in the pathology in most cases.

For the cells with just 1 or 2 of the common CNAs I think they likely provide a selective advantage to cells, or at least are not very deleterious relative to other CNAs.

Thanks to all co-authors, in particular @mike-oli.bsky.social, Vinci Au, Sam Aparicio, Joan Brugge and Sohrab Shah. This was a fascinating dataset to explore together!

We also found a very rare subset of cells that had extreme levels of aneuploidy, and to our eyes, were largely indistinguishable from breast cancer genomes.

These changes are strikingly similar to some common alterations found in breast cancers (gains of 1q, losses on 16q, 22)

We found chromosomal abnormalities occur at a low but appreciable level in all individuals (both BRCA carriers and non-carriers).

Luminal breast epithelial cells of BRCA1 or BRCA2 mutation carriers and noncarriers harbor common breast cancer copy number alterations - Nature Genetics Single-cell DNA sequencing identifies recurrent copy number changes in healthy breast tissue from women with wild-type or germline BRCA1 or BRCA2 mutations.

Our paper on chromosomal abnormalities in normal breast tissue from BRCA carriers came out last week.
www.nature.com/articles/s41...