Open AccessThe mutational signature profile of known and suspected human carcinogens in mice
Author(s) -
Laura Riva,
Arun R. Pandiri,
Yun R. Li,
Alastair Droop,
James Hewinson,
Michael A. Quail,
Vivek Iyer,
Rebecca Shepherd,
Ronald A. Herbert,
Peter J. Campbell,
Robert C. Sills,
Ludmil B. Alexandrov,
Allan Balmain,
David J. Adams
Publication year - 2020
Publication title -
nature genetics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 18.861
H-Index - 573
eISSN - 1546-1718
pISSN - 1061-4036
DOI - 10.1038/s41588-020-0692-4
Subject(s) - biology , compendium , carcinogen , genome , human genome , human health , genetics , mutation , gene , computational biology , environmental health , medicine , history , archaeology
Epidemiological studies have identified many environmental agents that appear to significantly increase cancer risk in human populations. By analyzing tumor genomes from mice chronically exposed to 1 of 20 known or suspected human carcinogens, we reveal that most agents do not generate distinct mutational signatures or increase mutation burden, with most mutations, including driver mutations, resulting from tissue-specific endogenous processes. We identify signatures resulting from exposure to cobalt and vinylidene chloride and link distinct human signatures (SBS19 and SBS42) with 1,2,3-trichloropropane, a haloalkane and pollutant of drinking water, and find these and other signatures in human tumor genomes. We define the cross-species genomic landscape of tumors induced by an important compendium of agents with relevance to human health.