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Evolutionary Dynamics of Non-Coding Regions in Pancreatic Ductal Adenocarcinoma

Hayashi, A.; Ho, Y.-j.; Makohon-Moore, A. P.; Zucker, A.; Hong, J.; Reiter, J. G.; Huang, J.; Zhang, L.; Attiyeh, M. A.; Baez, P.; Kappagantula, R.; Melchor, J. P.; OReilly, E. M.; Socci, N. D.; Oki, S.; Lowe, S.; Iacobuzio-Donahue, C. A.

2020-09-12 cancer biology
10.1101/2020.09.11.294389 bioRxiv
Show abstract

While the non-coding genome appears to play a role, the dynamic nature of noncoding alterations with respect to clonal progression of solid tumors remains unexplored. To address this gap in knowledge we performed multiregional whole genome sequencing and clonal analysis to elucidate the evolutionary dynamics of non-coding regions in pancreatic cancer relative to those of the coding genome. We find that the mutational burden of noncoding DNA is higher than coding DNA. However, when noncoding DNA was segregated into enhancer and non-enhancer regions, enhancers were more similar to coding DNA. Mutational signatures of noncoding and coding DNA further revealed the similar mutational spectra of enhancers to coding DNA whereas the mutational spectra of non-enhancer, noncoding DNA had an entirely different pattern. These findings shed light on the role of noncoding DNA in pancreatic cancer.

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"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.