Article
Oncology
Dominik Schulz, Guido Piontek, Ulrich M. Zissler, Gabriele Multhoff, Markus Wirth, Anja Pickhard
Summary: Resistance to chemotherapy is a major challenge in treating metastatic cancer, with tumor heterogeneity caused by genetic instability being a key contributing factor. Research shows that treatment with EGFR inhibitors or cisplatin induces genetic instability in head and neck squamous cancer cells, and combining these treatments with MEK1/2 inhibition significantly lowers mutation frequency.
AMERICAN JOURNAL OF CANCER RESEARCH
(2021)
Article
Cell Biology
Chunyan Zong, Zhe Zhang, Li Gao, Jie He, Yiran Wang, Qian Li, Xiaoting Liu, Jie Yang, Di Chen, Rui Huang, Guopei Zheng, Xiaoliang Jin, Wu Wei, Renbing Jia, Jianfeng Shen
Summary: APOBEC3B is an important mutation driver in cancer, promoting genomic instability through C-to-T conversion and replication stress (RS). This study reveals that APOBEC3B interacts with R-loops, RNA:DNA hybrid structures, promoting RS and altering their genomic distribution. This mechanism is dependent on the R-loop gatekeeper RNASEH1, and high levels of APOBEC3B confer sensitivity to ATR/Chk1 inhibitors in melanoma cells, depending on R-loop status. These findings have important implications for predicting patient response to ATR/Chk1 inhibitors.
CELL DEATH & DISEASE
(2023)
Article
Oncology
Jia-Wern Pan, Muhammad Mamduh Ahmad Zabidi, Boon-Keat Chong, Mei-Yee Meng, Pei-Sze Ng, Siti Norhidayu Hasan, Bethan Sandey, Saira Bahnu, Pathmanathan Rajadurai, Cheng-Har Yip, Oscar M. Rueda, Carlos Caldas, Suet-Feung Chin, Soo-Hwang Teo
Summary: In Asian women, the APOBEC3B deletion polymorphism leads to increased APOBEC-associated somatic hypermutation through the production of the A3A-B hybrid isoform, resulting in hypermutated tumors associated with the Her2 molecular subtype and PIK3CA mutations, as well as higher neoantigen burden, tumor heterogeneity, and immune activation.
INTERNATIONAL JOURNAL OF CANCER
(2021)
Article
Multidisciplinary Sciences
Christina Papini, Zechen Wang, Shalley N. Kudalkar, Travis Parke Schrank, Su Tang, Tomoaki Sasaki, Cory Wu, Brandon Tejada, Samantha J. Ziegler, Yong Xiong, Natalia Issaeva, Wendell G. Yarbrough, Karen S. Anderson
Summary: APOBEC3 family members are cytidine deaminases that play a role in cancer development and progression. Our study explored the kinetic features of A3A and A3B and found that they have different substrate preferences and purine sequence preferences. In HPV+ HNSCC, the catalytic activity of A3B and its preference for purine sequences were found to be more important than A3A. This study provides insights into APOBEC3-related carcinogenesis and facilitates drug discovery.
Article
Microbiology
Noemie Lejeune, Sarah A. Mathieu, Alexandra F. Decloux, Florian Poulain, Zoe F. Blockx, Kyle Raymond, Kevin F. Willemart, Jean-Pierre Vartanian, Rodolphe F. Suspene, Nicolas Gillet
Summary: This study reveals that APOBEC3B restricts the replication and propagation of adenoviruses by introducing clustered mutations into the viral genome. The efficiency of APOBEC3B restriction varies among different adenoviral strains. Adenovirus infection also leads to a decrease in the quantity and/or enzymatic activity of APOBEC3B protein. These findings suggest the evolution of mechanisms by adenoviruses to antagonize APOBEC3B, and the potential involvement of certain adenoviral strains in APOBEC3B dysregulation.
Article
Genetics & Heredity
Michael A. Carpenter, Nuri A. Temiz, Mahmoud A. Ibrahim, Matthew C. Jarvis, Margaret R. Brown, Prokopios P. Argyris, William L. Brown, Gabriel J. Starrett, Douglas Yee, Reuben S. Harris
Summary: The single-stranded DNA cytosine deamination by APOBEC3 enzymes is a significant source of mutation in cancer, and both APOBEC3A and APOBEC3B contribute to the overall mutation landscape.
Article
Oncology
Xiaoran Long, Huaiwu Lu, Mei-Chun Cai, Jingyu Zang, Zhuqing Zhang, Jie Wu, Xiaoshi Liu, Lin Cheng, Jiejun Cheng, Lydia W. T. Cheung, Zhen Shen, Ying Zhou, Wen Di, Guanglei Zhuang, Xia Yin
Summary: APOBEC3B is identified as a novel mechanism of stratification for ovarian clear cell carcinoma (OCCC) with favorable prognosis. Increased lymphocytic infiltration and immunogenicity were observed in APOBEC+ OCCC. Similar phenomena were also observed in endometriotic tissues, suggesting early occurrence of APOBEC-induced mutagenesis and immunogenicity in OCCC pathogenesis.
BRITISH JOURNAL OF CANCER
(2023)
Review
Oncology
Xingyue Yang, Jing Dai, Shun Yao, Jiaxing An, Guorong Wen, Hai Jin, Li Zhang, Liming Zheng, Xingyue Chen, Zhiqiang Yi, Biguang Tuo
Summary: Liver cancer is a common type of cancer worldwide, with hepatitis B virus infection being a major risk factor. APOBEC3B, a cytosine deaminase, has been found to be upregulated in various types of tumors. This review explores the role of APOBEC3B in the development of liver cancer due to HBV infection, providing new directions and strategies for the treatment and prevention of liver cancer.
FRONTIERS IN ONCOLOGY
(2022)
Article
Genetics & Heredity
Jennifer L. McCann, Agnese Cristini, Emily K. Law, Seo Yun Lee, Michael Tellier, Michael A. Carpenter, Chiara Beghe, Jae Jin Kim, Anthony Sanchez, Matthew C. Jarvis, Bojana Stefanovska, Nuri A. Temiz, Erik N. Bergstrom, Daniel J. Salamango, Margaret R. Brown, Shona Murphy, Ludmil B. Alexandrov, Kyle M. Miller, Natalia Gromak, Reuben S. Harris
Summary: The study reveals the interaction between APOBEC3B and R-loop factors, suggesting its role in regulating R-loops and contributing to R-loop mutagenesis in cancer.
Article
Cell Biology
Cameron Durfee, Nuri Alpay Temiz, Rena Levin-Klein, Prokopios P. Argyris, Lene Alsoe, Sergio Carracedo, Alicia Alonso de la Vega, Joshua Proehl, Anna M. Holzhauer, Zachary J. Seeman, Xingyu Liu, Yu-Hsiu T. Lin, Rachel I. Vogel, Rocio Sotillo, Hilde Nilsen, Reuben S. Harris
Summary: The antiviral DNA cytosine deaminase APOBEC3B has been found to play an important role in many cancer mutations. By studying a mouse model, it has been demonstrated that human APOBEC3B can drive tumor initiation and evolution in vivo.
CELL REPORTS MEDICINE
(2023)
Article
Oncology
Chuanhao Zhang, Zhichao Cheng, Zhe Wang, Genghao Zhao, Yonghui Yuan, Ruoyu Wang
Summary: This study reveals a positive relationship between APOBEC3B (A3B) and tumor mutational burden and microsatellite instability. A3B is also correlated with immune cell infiltration and immune checkpoint expression in bladder cancer. High expression of A3B may indicate a better response to immunotherapy, and the combination of A3B and CD274 can effectively predict response to immunotherapy in bladder urothelial carcinoma.
JOURNAL OF ONCOLOGY
(2022)
Article
Virology
Heng Tang, Ozlem Demir, Fredy Kurniawan, William L. Brown, Ke Shi, Nicholas H. Moeller, Michael A. Carpenter, Christopher Belica, Kayo Orellana, Guocheng Du, Aaron M. LeBeau, Rommie E. Amaro, Reuben S. Harris, Hideki Aihara
Summary: APOBEC3B is a crucial factor in limiting viral infections and driving tumor evolution, and the high-affinity antibody 5G7 offers specific detection of A3B, making it valuable for research and diagnostic applications.
Article
Biochemistry & Molecular Biology
Manikandan Periyasamy, Anup K. Singh, Carolina Gemma, Raed Farzan, Rebecca C. Allsopp, Jacqueline A. Shaw, Sara Charmsaz, Leonie S. Young, Paula Cunnea, R. Charles Coombes, Balazs Gyorffy, Lakjaya Buluwela, Simak Ali
Summary: Chemotherapeutic drugs can induce A3B expression independently of p53, mainly through the activation of DNA repair and NF-κB pathways. The expression of A3B contributes to chemotherapy resistance and can potentially accelerate cancer mutations.
Article
Engineering, Environmental
Rongrong Fan, Lin Xu, Bowen Cui, Daochuan Li, Xueying Sun, Yuan Qi, Jianan Rao, Kai Wang, Cheng Wang, Kunming Zhao, Yanjie Zhao, Juncheng Dai, Wen Chen, Hongbing Shen, Yu Liu, Dianke Yu
Summary: This study found that fine particulate matter (PM2.5) exposure causes DNA mutations and abnormal gene expression leading to lung cancer. The mechanisms behind this association are still unknown. Through analyzing genomic and transcriptomic changes in a human bronchial epithelial cell-based model, it was discovered that PM2.5 exposure led to APOBEC mutational signatures and transcriptional activation of APOBEC3B and other potential oncogenes. Additionally, it was observed that in non-small cell lung cancers (NSCLCs) from Chinese cohorts, there was a higher prevalence of APOBEC mutational signatures in non-smoking NSCLCs compared to smoking NSCLCs.
ENVIRONMENTAL SCIENCE & TECHNOLOGY
(2023)
Article
Oncology
Siyu Xia, Yun Gu, Haijian Zhang, Yuchao Fei, Yifan Cao, Hanji Fang, Jieti Wang, Chao Lin, Heng Zhang, He Li, Hongyong He, Jiejie Xu, Ruochen Li, Hao Liu, Weijuan Zhang
Summary: APOBEC3B serves an important role in tumor mutagenesis, and its high expression indicates poorer prognosis in gastric cancer patients. The tumor microenvironment of APOBEC3B-enriched tumors is characterized by reduced infiltration of CD8(+) T cells, but patients with high APOBEC3B and CD8(+) T cell levels may benefit from PD-1 blockade therapy.
