Tongwu Zhang, Jian Sang, Phuc H Hoang, Wei Zhao, Jennifer Rosenbaum, Kofi Ennu Johnson, Leszek J Klimczak, John McElderry, Alyssa Klein, Christopher Wirth, Erik N Bergstrom, Marcos Díaz-Gay, Raviteja Vangara, Frank Colon-Matos, Amy Hutchinson, Scott M Lawrence, Nathan Cole, Bin Zhu, Teresa M Przytycka, Jianxin Shi, Neil E Caporaso, Robert Homer, Angela C Pesatori, Dario Consonni, Marcin Imielinski, Stephen J Chanock, David C Wedge, Dmitry A Gordenin, Ludmil B Alexandrov, Reuben S Harris, Maria Teresa Landi
APOBEC enzymes are part of the innate immunity and are responsible for restricting viruses and retroelements by deaminating cytosine residues 1,2 . Most solid tumors harbor different levels of somatic mutations attributed to the off-target activities of APOBEC3A (A3A) and/or APOBEC3B (A3B) 3-6 . However, how APOBEC3A/B enzymes shape the tumor evolution in the presence of exogenous mutagenic processes is largely unknown. Here, by combining deep whole-genome sequencing with multi-omics profiling of 309 lung cancers from smokers with detailed tobacco smoking information, we identify two subtypes defined by low ( LAS ) and high ( HAS ) APOBEC mutagenesis...
April 3, 2024: bioRxiv