Naslov
Mutational Landscapes of Cancer Genomes Serve as Records of Early Malignant Transformation

Autori
Karlić, Rosa

Vrsta, podvrsta i kategorija rada
Sažeci sa skupova, neobjavljeni rad, znanstveni

Skup
NGS School 2019: Machine Learning for Biomedicine

Mjesto i datum
Białobrzegi, Poljska, 24.10.2019. - 31.10.2019

Vrsta sudjelovanja
Pozvano predavanje

Vrsta recenzije
Nije recenziran

Ključne riječi
Cancer genomics ; Cell-of-origin

Sažetak
A fundamental question in cancer biology is how the cell lineage influences the cell’s susceptibility to malignant transformation. Cell properties are encoded in the cell type-specific chromatin structure and we previously demonstrated that the landscape of somatic mutations in cancer is associated with the chromatin marks of the cell-of-origin (Polak et al, Nature, 2015). Many of these mutations accumulate before malignant transformation and serve as a historical record of the original normal cell. I will present the results of a recent pan-cancer study in which we searched for the putative cancer cell-of-origin of 2, 550 whole genomes, representing 32 cancer types by matching their mutational landscape to the regional patterns of chromatin modifications ascertained in 104 normal tissue types. Using a random forest regression model, we found that, in almost all cancer types, the cell-of-origin can be predicted solely from their DNA sequences. We also demonstrated that the technique is equally capable of identifying the cell-of-origin for a series of 2, 044 metastatic samples from 22 of the tumor types available as primaries. Moreover, cancer drivers, whether inherited or acquired, reside in active chromatin regions in the respective cell-of-origin. Taken together, these findings highlight that many somatic mutations accumulate while the chromatin structure of the cell-of-origin is maintained and that this historical record, captured in the DNA, can be used to identify the often elusive cancer cell-of-origin.

Izvorni jezik
Engleski

Znanstvena područja
Biologija

POVEZANOST RADA