دورية أكاديمية
The DNA Cytosine Deaminase APOBEC3B is a Molecular Determinant of Platinum Responsiveness in Clear Cell Ovarian Cancer.
العنوان: | The DNA Cytosine Deaminase APOBEC3B is a Molecular Determinant of Platinum Responsiveness in Clear Cell Ovarian Cancer. |
---|---|
المؤلفون: | Serebrenik AA; Department of Biochemistry, Molecular Biology and Biophysics, College of Biological Sciences, University of Minnesota, Minneapolis, Minnesota.; Masonic Cancer Center, University of Minnesota, Minneapolis, Minnesota.; Institute for Molecular Virology, University of Minnesota, Minneapolis, Minnesota.; Center for Genome Engineering, University of Minnesota, Minneapolis, Minnesota., Argyris PP; Department of Biochemistry, Molecular Biology and Biophysics, College of Biological Sciences, University of Minnesota, Minneapolis, Minnesota.; Masonic Cancer Center, University of Minnesota, Minneapolis, Minnesota.; Institute for Molecular Virology, University of Minnesota, Minneapolis, Minnesota.; Center for Genome Engineering, University of Minnesota, Minneapolis, Minnesota.; Division of Oral and Maxillofacial Pathology, School of Dentistry, University of Minnesota, Minneapolis, Minnesota., Jarvis MC; Department of Biochemistry, Molecular Biology and Biophysics, College of Biological Sciences, University of Minnesota, Minneapolis, Minnesota.; Masonic Cancer Center, University of Minnesota, Minneapolis, Minnesota.; Institute for Molecular Virology, University of Minnesota, Minneapolis, Minnesota.; Center for Genome Engineering, University of Minnesota, Minneapolis, Minnesota., Brown WL; Department of Biochemistry, Molecular Biology and Biophysics, College of Biological Sciences, University of Minnesota, Minneapolis, Minnesota.; Masonic Cancer Center, University of Minnesota, Minneapolis, Minnesota.; Institute for Molecular Virology, University of Minnesota, Minneapolis, Minnesota.; Center for Genome Engineering, University of Minnesota, Minneapolis, Minnesota., Bazzaro M; Department of Obstetrics, Gynecology and Women's Health, University of Minnesota, Minneapolis, Minnesota., Vogel RI; Masonic Cancer Center, University of Minnesota, Minneapolis, Minnesota.; Department of Obstetrics, Gynecology and Women's Health, University of Minnesota, Minneapolis, Minnesota., Erickson BK; Masonic Cancer Center, University of Minnesota, Minneapolis, Minnesota.; Department of Obstetrics, Gynecology and Women's Health, University of Minnesota, Minneapolis, Minnesota., Lee SH; Department of Oncology, Mayo Clinic, Rochester, Minnesota., Goergen KM; Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota., Maurer MJ; Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota., Heinzen EP; Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota., Oberg AL; Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota., Huang Y; Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota., Hou X; Department of Oncology, Mayo Clinic, Rochester, Minnesota., Weroha SJ; Department of Oncology, Mayo Clinic, Rochester, Minnesota., Kaufmann SH; Department of Oncology, Mayo Clinic, Rochester, Minnesota., Harris RS; Department of Biochemistry, Molecular Biology and Biophysics, College of Biological Sciences, University of Minnesota, Minneapolis, Minnesota. rsh@umn.edu.; Masonic Cancer Center, University of Minnesota, Minneapolis, Minnesota.; Institute for Molecular Virology, University of Minnesota, Minneapolis, Minnesota.; Center for Genome Engineering, University of Minnesota, Minneapolis, Minnesota.; Howard Hughes Medical Institute, University of Minnesota, Minneapolis, Minnesota. |
المصدر: | Clinical cancer research : an official journal of the American Association for Cancer Research [Clin Cancer Res] 2020 Jul 01; Vol. 26 (13), pp. 3397-3407. Date of Electronic Publication: 2020 Feb 14. |
نوع المنشور: | Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't |
اللغة: | English |
بيانات الدورية: | Publisher: The Association Country of Publication: United States NLM ID: 9502500 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1557-3265 (Electronic) Linking ISSN: 10780432 NLM ISO Abbreviation: Clin Cancer Res Subsets: MEDLINE |
أسماء مطبوعة: | Original Publication: Denville, NJ : The Association, c1995- |
مواضيع طبية MeSH: | Cytidine Deaminase/*metabolism , Minor Histocompatibility Antigens/*metabolism , Ovarian Neoplasms/*metabolism , Platinum/*pharmacology, Animals ; Antineoplastic Agents/pharmacology ; Biomarkers, Tumor ; Cell Line, Tumor ; Cell Survival/drug effects ; Cell Survival/genetics ; Cytidine Deaminase/genetics ; Disease Models, Animal ; Drug Resistance, Neoplasm ; Female ; Gene Expression ; Humans ; Immunohistochemistry ; Kaplan-Meier Estimate ; Mice ; Minor Histocompatibility Antigens/genetics ; Ovarian Neoplasms/drug therapy ; Ovarian Neoplasms/mortality ; Ovarian Neoplasms/pathology ; Prognosis ; Synthetic Lethal Mutations/drug effects ; Synthetic Lethal Mutations/genetics ; Xenograft Model Antitumor Assays |
مستخلص: | Purpose: Clear cell ovarian carcinoma (CCOC) is an aggressive disease that often demonstrates resistance to standard chemotherapies. Approximately 25% of patients with CCOC show a strong APOBEC mutation signature. Here, we determine which APOBEC3 enzymes are expressed in CCOC, establish clinical correlates, and identify a new biomarker for detection and intervention. Experimental Designs: APOBEC3 expression was analyzed by IHC and qRT-PCR in a pilot set of CCOC specimens ( n = 9 tumors). The IHC analysis of APOBEC3B was extended to a larger cohort to identify clinical correlates ( n = 48). Dose-response experiments with platinum-based drugs in CCOC cell lines and carboplatin treatment of patient-derived xenografts (PDXs) were done to address mechanistic linkages. Results: One DNA deaminase, APOBEC3B, is overexpressed in a formidable subset of CCOC tumors and is low or absent in normal ovarian and fallopian tube epithelial tissues. High APOBEC3B expression associates with improved progression-free survival ( P = 0.026) and moderately with overall survival ( P = 0.057). Cell-based studies link APOBEC3B activity and subsequent uracil processing to sensitivity to cisplatin and carboplatin. PDX studies extend this mechanistic relationship to CCOC tissues. Conclusions: These studies demonstrate that APOBEC3B is overexpressed in a subset of CCOC and, contrary to initial expectations, associated with improved (not worse) clinical outcomes. A likely molecular explanation is that APOBEC3B-induced DNA damage sensitizes cells to additional genotoxic stress by cisplatin. Thus, APOBEC3B is a molecular determinant and a candidate predictive biomarker of the therapeutic response to platinum-based chemotherapy. These findings may have broader translational relevance, as APOBEC3B is overexpressed in many different cancer types. (©2020 American Association for Cancer Research.) |
References: | Proc Natl Acad Sci U S A. 2019 Oct 29;116(44):22158-22163. (PMID: 31611371) Cancer Res. 2017 Sep 1;77(17):4567-4578. (PMID: 28698210) J Biol Chem. 2012 Jul 13;287(29):24263-72. (PMID: 22621925) Nature. 2011 Jun 29;474(7353):609-15. (PMID: 21720365) PLoS One. 2013 Sep 04;8(9):e72162. (PMID: 24023729) Gynecol Oncol. 2012 Sep;126(3):481-90. (PMID: 22525820) Cancer Res. 2017 Sep 1;77(17):4579-4588. (PMID: 28655787) J Virol. 2009 Sep;83(18):9474-85. (PMID: 19587057) Cell Rep. 2013 Dec 12;5(5):1256-68. (PMID: 24316072) Front Oncol. 2018 Feb 05;8:16. (PMID: 29459887) Br J Cancer. 2017 Jun 27;117(1):113-123. (PMID: 28535155) Nature. 2013 Feb 21;494(7437):366-70. (PMID: 23389445) Clin Cancer Res. 2016 Sep 15;22(18):4746-55. (PMID: 27016308) Cancer Epidemiol Biomarkers Prev. 2017 Oct;26(10):1511-1518. (PMID: 28751475) Nat Genet. 2014 May;46(5):487-91. (PMID: 24728294) Gynecol Oncol. 1999 Jul;74(1):108-14. (PMID: 10385560) Cancer Sci. 2008 Apr;99(4):653-8. (PMID: 18377417) Sci Adv. 2016 Oct 07;2(10):e1601737. (PMID: 27730215) J Clin Pathol. 2014 Oct;67(10):921-2. (PMID: 25049276) Cancer Discov. 2015 Jul;5(7):704-12. (PMID: 26091828) Cancer Res. 2013 Dec 15;73(24):7222-31. (PMID: 24154874) J Mol Biol. 2018 Aug 17;430(17):2695-2708. (PMID: 29787764) Genes Chromosomes Cancer. 2018 Feb;57(2):51-60. (PMID: 29044863) Mol Cancer Ther. 2013 Jun;12(6):1002-15. (PMID: 23729402) J Biol Chem. 2011 Apr 22;286(16):14564-74. (PMID: 21357694) Nat Commun. 2013;4:2126. (PMID: 23839242) Neoplasia. 2017 Aug;19(8):628-636. (PMID: 28658648) Am J Cancer Res. 2015 Apr 15;5(5):1751-61. (PMID: 26175943) Nat Genet. 2015 Sep;47(9):1067-72. (PMID: 26258849) Cancer Res. 2015 Nov 1;75(21):4538-47. (PMID: 26420215) Methods. 2019 Mar 1;156:79-84. (PMID: 30578845) Cancer Res. 2017 Nov 1;77(21):e62-e66. (PMID: 29092942) Breast Cancer Res. 2015 Jan 21;17:8. (PMID: 25848704) J Virol. 2008 Oct;82(19):9591-9. (PMID: 18667511) Comp Med. 2009 Jun;59(3):234-41. (PMID: 19619413) Horm Cancer. 2014 Dec;5(6):405-13. (PMID: 25123150) Nat Commun. 2016 Sep 21;7:12918. (PMID: 27650891) Clin Cancer Res. 2014 Mar 1;20(5):1288-97. (PMID: 24398046) PLoS One. 2014 Dec 08;9(12):e114051. (PMID: 25485635) J Pathol. 2018 Apr;244(5):550-564. (PMID: 29344971) Nat Genet. 2017 Jun;49(6):856-865. (PMID: 28436987) Nat Genet. 2013 Sep;45(9):977-83. (PMID: 23852168) J Cancer. 2016 Mar 19;7(6):618-25. (PMID: 27076842) JNCI Cancer Spectr. 2018 Jan;2(1):. (PMID: 29888758) Antibodies (Basel). 2019 Sep 10;8(3):. (PMID: 31544853) Histol Histopathol. 2019 Apr;34(4):405-417. (PMID: 30289149) Urol Oncol. 2015 Aug;33(8):340.e1-8. (PMID: 26051357) Nucleic Acids Res. 2010 Jul;38(13):4274-84. (PMID: 20308164) J Biol Chem. 2013 Jun 14;288(24):17253-60. (PMID: 23640892) |
معلومات مُعتمدة: | K12 HD055887 United States HD NICHD NIH HHS; P30 CA077598 United States CA NCI NIH HHS; United States HHMI Howard Hughes Medical Institute; T32 CA009138 United States CA NCI NIH HHS; P01 CA234228 United States CA NCI NIH HHS; P50 CA136393 United States CA NCI NIH HHS; R01 GM130800 United States GM NIGMS NIH HHS; UL1 TR002494 United States TR NCATS NIH HHS |
المشرفين على المادة: | 0 (Antineoplastic Agents) 0 (Biomarkers, Tumor) 0 (Minor Histocompatibility Antigens) 49DFR088MY (Platinum) EC 3.5.4.5 (APOBEC3B protein, human) EC 3.5.4.5 (Cytidine Deaminase) |
تواريخ الأحداث: | Date Created: 20200216 Date Completed: 20210914 Latest Revision: 20240214 |
رمز التحديث: | 20240214 |
مُعرف محوري في PubMed: | PMC7334080 |
DOI: | 10.1158/1078-0432.CCR-19-2786 |
PMID: | 32060098 |
قاعدة البيانات: | MEDLINE |
تدمد: | 1557-3265 |
---|---|
DOI: | 10.1158/1078-0432.CCR-19-2786 |