Naslov
The impact of chromatin on mutation rate

Autori
Polak, Paz ; Karlić, Rosa ; Koren, Amnon ; Thurman, Robert ; Sandstrom, Richard ; Lawrence, Michael S. ; Reynolds, Alex ; Rynes, Eric ; Vlahoviček, Kristian ; Stamatoyannopoulos, John A. ; Sunyaev, Shamil R.

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

Skup
American Society of Human Genetics Meeting

Mjesto i datum
San Diego (CA), Sjedinjene Američke Države, 18.10.2015. - 22.10.2015

Vrsta sudjelovanja
Predavanje

Vrsta recenzije
Međunarodna recenzija

Ključne riječi
cancer ; mutional density ; chromatin ; epigenomics

Sažetak
Cancer is a disease potentiated by mutations in somatic cells. Cancer mutations are not distributed uniformly along the human genome. Instead, different human genomic regions vary by up to fivefold in the local density of cancer somatic mutations, posing a fundamental problem for statistical methods used in cancer genomics. Epigenomic organization has been proposed as a major determinant of the cancer mutational landscape. However, both somatic mutagenesis and epigenomic features are highly cell-type-specific. We investigated the distribution of mutations in multiple independent samples of diverse cancer types and compared them to cell-type-specific epigenomic features. Here we show that chromatin accessibility and modification, together with replication timing, explain up to 86% of the variance in mutation rates along cancer genomes. The best predictors of local somatic mutation density are epigenomic features derived from the most likely cell type of origin of the corresponding malignancy. Moreover, we find that cell-of-origin chromatin features are much stronger determinants of cancer mutation profiles than chromatin features of matched cancer cell lines. Furthermore, we show that the cell type of origin of a cancer can be accurately determined based on the distribution of mutations along its genome. Thus, the DNA sequence of a cancer genome encompasses a wealth of information about the identity and epigenomic features of its cell of origin.

Izvorni jezik
Engleski

Znanstvena područja
Biologija

POVEZANOST RADA