Exploring the Regulation of Apobac 3B and GaTA-3 in Adrenocortical Carcinoma

The cover for issue 36 of Oncotarget features Figure 7, "Knockdown of APOBEC3B is associated with a lower tumor growth in an adrenocortical carcinoma xenograft mouse model," by Gara, et al. which reported that the role of APOBEC3B in adrenocortical carcinoma and the mechanisms through which its expression is regulated in cancer are not fully understood. Here, the authors report that APOBEC3B is overexpressed in ACC and it regulates cell proliferation by inducing S phase arrest. They show high APOBEC3B expression is associated with a higher copy number gain/loss at chromosome 4 and 8 and TP53 mutation rate in ACC. GATA3 was identified as a positive regulator of APOBEC3B expression and directly binds the APOBEC3B promoter region. Both GATA3 and APOBEC3B expression levels were associated with patient survival. This Oncotarget study provides novel insights into the function and regulation of APOBEC3B expression in addition to its known mutagenic ability. Dr. Electron Kebebew from Stanford University said, "Adrenocortical carcinoma (ACC) is a rare and aggressive endocrine malignancy." The distinct pattern of DNA base alterations has been characterized in the cancer genome using high throughput deep sequencing technologies, that reflect the underlying mutational process. Whole-genome and exome mutation analysis of The Cancer Genome Atlas data on multiple cancers has revealed that this pattern is consistent with the deaminase activity of the AID/APOBEC family of enzymes, therefore, implying its significance as an endogenous mutator and a crucial contributor to somatic mutations and genomic instability. APOBEC3B is overexpressed in ovarian cancer cell lines and high-grade primary ovarian cancers. In addition, APOBEC3B expression is positively correlated with the total mutation load, as well as, elevated levels of transversion mutations. Given there are no well-established exogenous factors associated with ACC, the Oncotarget authors postulated whether APOBEC3B could be an endogenous mechanism of genomic instability/mutations in ACC and investigated its function in vitro and in vivo. The Kebebew Research Team concluded in their Oncotarget Research Paper, "APOBEC3B overexpressed in ACC, and is associated with DNA damage, S phase arrest, higher copy number alterations and TP53 mutations in ACC. For the first time, we demonstrated that GATA3 directly regulates the expression of APOBEC3B and that both are prognostic markers in ACC." Sign up for free Altmetric alerts about this article DOI - https://doi.org/10.18632/oncotarget.27703 Full text - https://www.oncotarget.com/article/27703/text/ Correspondence to - Electron Kebebew - kebebew@stanford.edu Keywords - adrenocortical carcinoma, APOBEC3B, GATA3, prognosis, DNA damage About Oncotarget Oncotarget is a peer-reviewed, open access biomedical journal covering research on all aspects of oncology. To learn more about Oncotarget, please visit https://www.oncotarget.com or connect with: SoundCloud - https://soundcloud.com/oncotarget Facebook - https://www.facebook.com/Oncotarget/ Twitter - https://twitter.com/oncotarget LinkedIn - https://www.linkedin.com/company/oncotarget Pinterest - https://www.pinterest.com/oncotarget/ Reddit - https://www.reddit.com/user/Oncotarget/ Oncotarget is published by Impact Journals, LLC please visit http://www.ImpactJournals.com or connect with @ImpactJrnls Media Contact MEDIA@IMPACTJOURNALS.COM 18009220957x105 Copyright © 2021 Impact Journals, LLC Impact Journals is a registered trademark of Impact Journals, LLC