Mutational signatures association with replication timing in normal cells reveals similarities and differences with matched cancer tissues

Adar Yaacov, Shai Rosenberg, Itamar Simon*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

3 Scopus citations

Abstract

Mutational signatures’ association with replication timing (RT) has been studied in cancer samples, but the RT distribution of somatic mutations in non-cancerous cells was only minimally explored. Here, we performed comprehensive analyses of mutational signatures in 2.9 million somatic mutations across multiple non-cancerous tissues, stratified by early and late RT regions. We found that many mutational processes are active mainly or solely in early RT, such as SBS16 in hepatocytes and SBS88 in the colon, or in late RT, such as SBS4 in lung and hepatocytes, and SBS18 across many tissues. The two ubiquitous signatures, SBS1 and SBS5, showed late and early bias, respectively, across multiple tissues and in mutations representing germ cells. We also performed a direct comparison with cancer samples in 4 matched tissue-cancer types. Unexpectedly, while for most signatures the RT bias was consistent in normal tissue and in cancer, we found that SBS1’s late RT bias is lost in cancer.

Original languageAmerican English
Article number7833
JournalScientific Reports
Volume13
Issue number1
DOIs
StatePublished - 15 May 2023

Bibliographical note

Publisher Copyright:
© 2023, The Author(s).

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