Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Article
  • Published:

Clinical Studies

APOBEC3B stratifies ovarian clear cell carcinoma with distinct immunophenotype and prognosis

British Journal of Cancer volume 128, pages 2054–2062 (2023)Cite this article

Subjects

Abstract

Background

Ovarian clear cell carcinoma (OCCC) is a challenging disease due to its intrinsic chemoresistance. Immunotherapy is an emerging treatment option but currently impeded by insufficient understanding of OCCC immunophenotypes and their molecular determinants.

Methods

Whole-genome sequencing on 23 pathologically confirmed patients was employed to depict the genomic profile of primary OCCCs. APOBEC3B expression and digital pathology-based Immunoscore were assessed by performing immunohistochemistry and correlated with clinical outcomes.

Results

An APOBEC-positive (APOBEC+) subtype was identified based on the characteristic mutational signature and prevalent kataegis events. APOBEC + OCCC displayed favourable prognosis across one internal and two external patient cohorts. The improved outcome was ascribable to increased lymphocytic infiltration. Similar phenomena of APOBEC3B expression and T-cell accumulation were observed in endometriotic tissues, suggesting that APOBEC-induced mutagenesis and immunogenicity could occur early during OCCC pathogenesis. Corroborating these results, a case report was presented for an APOBEC + patient demonstrating inflamed tumour microenvironment and clinical response to immune checkpoint blockade.

Conclusions

Our findings implicate APOBEC3B as a novel mechanism of OCCC stratification with prognostic value and as a potential predictive biomarker that may inform immunotherapeutic opportunities.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Fig. 1: WGS identifies an APOBEC + OCCC subtype.
Fig. 2: APOBEC + OCCC shows superior prognosis.
Fig. 3: APOBEC + OCCC has increased lymphocytic infiltration.
Fig. 4: Immune density and localisation impact patient survival.
Fig. 5: APOBEC + OCCC may benefit from immunotherapy.

Similar content being viewed by others

Data availability

The sequencing data generated in this study have been deposited in NCBI SRA database under the accession number SRP157148. All the other data and materials are available within the article or upon request from the corresponding authors.

References

  1. Karnezis AN, Cho KR, Gilks CB, Pearce CL, Huntsman DG. The disparate origins of ovarian cancers: pathogenesis and prevention strategies. Nat Rev Cancer. 2017;17:65–74.

    Article  CAS  PubMed  Google Scholar 

  2. Iida Y, Okamoto A, Hollis RL, Gourley C, Herrington CS. Clear cell carcinoma of the ovary: a clinical and molecular perspective. Int J Gynecol Cancer. 2021;31:605–16.

    Article  PubMed  Google Scholar 

  3. Khalique S, Lord CJ, Banerjee S, Natrajan R. Translational genomics of ovarian clear cell carcinoma. Semin Cancer Biol. 2020;61:121–31.

    Article  PubMed  Google Scholar 

  4. Itamochi H, Oishi T, Oumi N, Takeuchi S, Yoshihara K, Mikami M, et al. Whole-genome sequencing revealed novel prognostic biomarkers and promising targets for therapy of ovarian clear cell carcinoma. Br J Cancer. 2017;117:717–24.

    Article  CAS  PubMed  Google Scholar 

  5. Armstrong DK, Alvarez RD, Bakkum-Gamez JN, Barroilhet L, Behbakht K, Berchuck A, et al. Ovarian Cancer, Version 2.2020, NCCN Clinical Practice Guidelines in Oncology. J Natl Compr Cancer Netw. 2021;19:191–226.

    Article  CAS  Google Scholar 

  6. Yin X, Bi R, Ma P, Zhang S, Zhang Y, Sun Y, et al. Multiregion whole-genome sequencing depicts intratumour heterogeneity and punctuated evolution in ovarian clear cell carcinoma. J Med Genet. 2020;57:605–9.

    Article  CAS  PubMed  Google Scholar 

  7. Venkatesan S, Angelova M, Puttick C, Zhai H, Caswell DR, Lu WT, et al. Induction of APOBEC3 exacerbates DNA replication stress and chromosomal instability in early breast and lung cancer evolution. Cancer Discov. 2021;11:2456–73.

    Article  PubMed  Google Scholar 

  8. Swanton C, McGranahan N, Starrett GJ, Harris RS. APOBEC enzymes: mutagenic fuel for cancer evolution and heterogeneity. Cancer Discov. 2015;5:704–12.

    Article  CAS  PubMed  Google Scholar 

  9. Smid M, Rodriguez-Gonzalez FG, Sieuwerts AM, Salgado R, Prager-Van der Smissen WJ, Vlugt-Daane MV, et al. Breast cancer genome and transcriptome integration implicates specific mutational signatures with immune cell infiltration. Nat Commun. 2016;7:12910.

    Article  CAS  PubMed  Google Scholar 

  10. Driscoll CB, Schuelke MR, Kottke T, Thompson JM, Wongthida P, Tonne JM, et al. APOBEC3B-mediated corruption of the tumor cell immunopeptidome induces heteroclitic neoepitopes for cancer immunotherapy. Nat Commun. 2020;11:790.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Wang S, Jia M, He Z, Liu XS. APOBEC3B and APOBEC mutational signature as potential predictive markers for immunotherapy response in non-small cell lung cancer. Oncogene. 2018;37:3924–36.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Miao D, Margolis CA, Vokes NI, Liu D, Taylor-Weiner A, Wankowicz SM, et al. Genomic correlates of response to immune checkpoint blockade in microsatellite-stable solid tumors. Nat Genet. 2018;50:1271–81.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Matulonis UA, Shapira-Frommer R, Santin AD, Lisyanskaya AS, Pignata S, Vergote I, et al. Antitumor activity and safety of pembrolizumab in patients with advanced recurrent ovarian cancer: results from the phase II KEYNOTE-100 study. Ann Oncol. 2019;30:1080–7.

    Article  CAS  PubMed  Google Scholar 

  14. Zamarin D, Burger RA, Sill MW, Powell DJ Jr., Lankes HA, Feldman MD, et al. Randomized phase II trial of nivolumab versus nivolumab and ipilimumab for recurrent or persistent ovarian cancer: an NRG Oncology Study. J Clin Oncol. 2020;38:1814–23.

    Article  CAS  PubMed  Google Scholar 

  15. Hamanishi J, Mandai M, Ikeda T, Minami M, Kawaguchi A, Murayama T, et al. Safety and antitumor activity of anti-PD-1 antibody, nivolumab, in patients with platinum-resistant ovarian cancer. J Clin Oncol. 2015;33:4015–22.

    Article  CAS  PubMed  Google Scholar 

  16. Howitt BE, Strickland KC, Sholl LM, Rodig S, Ritterhouse LL, Chowdhury D, et al. Clear cell ovarian cancers with microsatellite instability: a unique subset of ovarian cancers with increased tumor-infiltrating lymphocytes and PD-1/PD-L1 expression. Oncoimmunology. 2017;6:e1277308.

    Article  PubMed  Google Scholar 

  17. Wang YK, Bashashati A, Anglesio MS, Cochrane DR, Grewal DS, Ha G, et al. Genomic consequences of aberrant DNA repair mechanisms stratify ovarian cancer histotypes. Nat Genet. 2017;49:856–65.

    Article  CAS  PubMed  Google Scholar 

  18. Shibuya Y, Tokunaga H, Saito S, Shimokawa K, Katsuoka F, Bin L, et al. Identification of somatic genetic alterations in ovarian clear cell carcinoma with next generation sequencing. Genes Chromosomes Cancer. 2018;57:51–60.

    Article  CAS  PubMed  Google Scholar 

  19. Oliveira D, Schnack TH, Poulsen TS, Christiansen AP, Hogdall CK, Hogdall EV. Genomic sub-classification of ovarian clear cell carcinoma revealed by distinct mutational signatures. Cancers (Basel). 2021;13:5242.

    Article  CAS  PubMed  Google Scholar 

  20. Pecori R, Di Giorgio S, Paulo Lorenzo J, Nina Papavasiliou F. Functions and consequences of AID/APOBEC-mediated DNA and RNA deamination. Nat Rev Genet. 2022;23:505–18.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Salter JD, Bennett RP, Smith HC. The APOBEC protein family: united by structure, divergent in function. Trends Biochem Sci. 2016;41:578–94.

    Article  CAS  PubMed Central  Google Scholar 

  22. Burns MB, Temiz NA, Harris RS. Evidence for APOBEC3B mutagenesis in multiple human cancers. Nat Genet. 2013;45:977–83.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Green AM, Weitzman MD. The spectrum of APOBEC3 activity: from anti-viral agents to anti-cancer opportunities. DNA Repair (Amst). 2019;83:102700.

    Article  CAS  PubMed  Google Scholar 

  24. Ng JCF, Quist J, Grigoriadis A, Malim MH, Fraternali F. Pan-cancer transcriptomic analysis dissects immune and proliferative functions of APOBEC3 cytidine deaminases. Nucleic Acids Res. 2019;47:1178–94.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Serebrenik AA, Argyris PP, Jarvis MC, Brown WL, Bazzaro M, Vogel RI, et al. The DNA cytosine deaminase APOBEC3B is a molecular determinant of platinum responsiveness in clear cell ovarian cancer. Clin Cancer Res. 2020;26:3397–407.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Maciejowski J, Chatzipli A, Dananberg A, Chu K, Toufektchan E, Klimczak LJ, et al. APOBEC3-dependent kataegis and TREX1-driven chromothripsis during telomere crisis. Nat Genet. 2020;52:884–90.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Consortium ITP-CAoWG. Pan-cancer analysis of whole genomes. Nature. 2020;578:82–93.

    Article  Google Scholar 

  28. Vile RG, Melcher A, Pandha H, Harrington KJ, Pulido JS. APOBEC and cancer viroimmunotherapy: thinking the unthinkable. Clin Cancer Res. 2021;27:3280–90.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Khalique S, Nash S, Mansfield D, Wampfler J, Attygale A, Vroobel K, et al. Quantitative assessment and prognostic associations of the immune landscape in ovarian clear cell carcinoma. Cancers (Basel). 2021;13:3854.

    Article  CAS  PubMed  Google Scholar 

  30. Galon J, Mlecnik B, Bindea G, Angell HK, Berger A, Lagorce C, et al. Towards the introduction of the ‘Immunoscore’ in the classification of malignant tumours. J Pathol. 2014;232:199–209.

    Article  CAS  PubMed  Google Scholar 

  31. Pages F, Mlecnik B, Marliot F, Bindea G, Ou FS, Bifulco C, et al. International validation of the consensus Immunoscore for the classification of colon cancer: a prognostic and accuracy study. Lancet. 2018;391:2128–39.

    Article  PubMed  Google Scholar 

  32. Angell HK, Bruni D, Barrett JC, Herbst R, Galon J. The immunoscore: colon cancer and beyond. Clin Cancer Res. 2020;26:332–9.

    Article  CAS  PubMed  Google Scholar 

  33. Bruni D, Angell HK, Galon J. The immune contexture and Immunoscore in cancer prognosis and therapeutic efficacy. Nat Rev Cancer. 2020;20:662–80.

    Article  CAS  PubMed  Google Scholar 

  34. Hegde PS, Karanikas V, Evers S. The where, the when, and the how of immune monitoring for cancer immunotherapies in the era of checkpoint inhibition. Clin Cancer Res. 2016;22:1865–74.

    Article  CAS  PubMed  Google Scholar 

  35. Revathidevi S, Nakaoka H, Suda K, Fujito N, Munirajan AK, Yoshihara K, et al. APOBEC mediated mutagenesis drives genomic heterogeneity in endometriosis. J Hum Genet. 2022;67:323–9.

  36. Leonard B, McCann JL, Starrett GJ, Kosyakovsky L, Luengas EM, Molan AM, et al. The PKC/NF-kappaB signaling pathway induces APOBEC3B expression in multiple human cancers. Cancer Res. 2015;75:4538–47.

    Article  CAS  PubMed  Google Scholar 

  37. Roper N, Gao S, Maity TK, Banday AR, Zhang X, Venugopalan A, et al. APOBEC mutagenesis and copy-number alterations are drivers of proteogenomic tumor evolution and heterogeneity in metastatic thoracic tumors. Cell Rep. 2019;26:2651–66 e2656.

    Article  CAS  PubMed  Google Scholar 

  38. Udquim KI, Zettelmeyer C, Banday AR, Lin SH, Prokunina-Olsson L. APOBEC3B expression in breast cancer cell lines and tumors depends on the estrogen receptor status. Carcinogenesis. 2020;41:1030–7.

    Article  CAS  PubMed  Google Scholar 

  39. Bader SB, Ma TS, Simpson CJ, Liang J, Maezono SEB, Olcina MM, et al. Replication catastrophe induced by cyclic hypoxia leads to increased APOBEC3B activity. Nucleic Acids Res. 2021;49:7492–506.

    Article  CAS  PubMed  Google Scholar 

  40. Petljak M, Alexandrov LB, Brammeld JS, Price S, Wedge DC, Grossmann S, et al. Characterizing mutational signatures in human cancer cell lines reveals episodic APOBEC mutagenesis. Cell. 2019;176:1282–94 e1220.

    Article  CAS  PubMed  Google Scholar 

  41. Kanu N, Cerone MA, Goh G, Zalmas LP, Bartkova J, Dietzen M, et al. DNA replication stress mediates APOBEC3 family mutagenesis in breast cancer. Genome Biol. 2016;17:185.

    Article  PubMed  Google Scholar 

  42. Petljak M, Maciejowski J. Molecular origins of APOBEC-associated mutations in cancer. DNA Repair (Amst). 2020;94:102905.

    Article  CAS  PubMed  Google Scholar 

  43. Gadducci A, Multinu F, Cosio S, Carinelli S, Ghioni M, Aletti GD. Clear cell carcinoma of the ovary: epidemiology, pathological and biological features, treatment options and clinical outcomes. Gynecol Oncol. 2021;162:741–50.

    Article  PubMed  Google Scholar 

  44. Grillo MJ, Jones KFM, Carpenter MA, Harris RS, Harki DA. The current toolbox for APOBEC drug discovery. Trends Pharm Sci. 2022;43:362–77.

    Article  CAS  PubMed  Google Scholar 

  45. Buisson R, Lawrence MS, Benes CH, Zou L. APOBEC3A and APOBEC3B activities render cancer cells susceptible to ATR inhibition. Cancer Res. 2017;77:4567–78.

    Article  CAS  PubMed  Google Scholar 

  46. Serebrenik AA, Starrett GJ, Leenen S, Jarvis MC, Shaban NM, Salamango DJ, et al. The deaminase APOBEC3B triggers the death of cells lacking uracil DNA glycosylase. Proc Natl Acad Sci USA. 2019;116:22158–63.

    Article  CAS  PubMed  Google Scholar 

  47. Ngoi NY, Heong V, Ow S, Chay WY, Kim HS, Choi CH, et al. A multicenter phase II randomized trial of durvalumab (MEDI-4736) versus physician’s choice chemotherapy in recurrent ovarian clear cell adenocarcinoma (MOCCA). Int J Gynecol Cancer. 2020;30:1239–42.

    Article  PubMed  Google Scholar 

  48. Oda K, Hamanishi J, Matsuo K, Hasegawa K. Genomics to immunotherapy of ovarian clear cell carcinoma: Unique opportunities for management. Gynecol Oncol. 2018;151:381–9.

    Article  CAS  PubMed  Google Scholar 

  49. Roberts SA, Lawrence MS, Klimczak LJ, Grimm SA, Fargo D, Stojanov P, et al. An APOBEC cytidine deaminase mutagenesis pattern is widespread in human cancers. Nat Genet. 2013;45:970–6.

    Article  CAS  PubMed  Google Scholar 

  50. Li H, Durbin R. Fast and accurate short read alignment with Burrows-Wheeler transform. Bioinformatics. 2009;25:1754–60.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Cibulskis K, Lawrence MS, Carter SL, Sivachenko A, Jaffe D, Sougnez C, et al. Sensitive detection of somatic point mutations in impure and heterogeneous cancer samples. Nat Biotechnol. 2013;31:213–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Saunders CT, Wong WS, Swamy S, Becq J, Murray LJ, Cheetham RK. Strelka: accurate somatic small-variant calling from sequenced tumor-normal sample pairs. Bioinformatics. 2012;28:1811–7.

    Article  CAS  PubMed  Google Scholar 

  53. Wang K, Li M, Hakonarson H. ANNOVAR: functional annotation of genetic variants from high-throughput sequencing data. Nucleic Acids Res. 2010;38:e164.

    Article  PubMed  PubMed Central  Google Scholar 

  54. Cun Y, Yang TP, Achter V, Lang U, Peifer M. Copy-number analysis and inference of subclonal populations in cancer genomes using Sclust. Nat Protoc. 2018;13:1488–501.

    Article  CAS  PubMed  Google Scholar 

  55. Wang J, Mullighan CG, Easton J, Roberts S, Heatley SL, Ma J, et al. CREST maps somatic structural variation in cancer genomes with base-pair resolution. Nat Methods. 2011;8:652–4.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Gehring JS, Fischer B, Lawrence M, Huber W. SomaticSignatures: inferring mutational signatures from single-nucleotide variants. Bioinformatics. 2015;31:3673–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Rubanova Y, Shi R, Harrigan CF, Li R, Wintersinger J, Sahin N, et al. Reconstructing evolutionary trajectories of mutation signature activities in cancer using TrackSig. Nat Commun. 2020;11:731.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Gu Z, Gu L, Eils R, Schlesner M, Brors B. circlize Implements and enhances circular visualization in R. Bioinformatics. 2014;30:2811–2.

    Article  CAS  PubMed  Google Scholar 

  59. Shukla SA, Rooney MS, Rajasagi M, Tiao G, Dixon PM, Lawrence MS, et al. Comprehensive analysis of cancer-associated somatic mutations in class I HLA genes. Nat Biotechnol. 2015;33:1152–8.

    Article  CAS  PubMed  Google Scholar 

  60. Jurtz V, Paul S, Andreatta M, Marcatili P, Peters B, Nielsen M. NetMHCpan-4.0: improved peptide-MHC class I interaction predictions integrating eluted ligand and peptide binding affinity data. J Immunol. 2017;199:3360–8.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

Not applicable.

Funding

This work was supported by the National Natural Science Foundation of China (82173077 and 82211540402 to XY; 81922047 and 82172596 to GZ; 81974454 to WD; 82022078 to LC), National Key Research and Development Program of China (2021YFC2700400 to WD), Shanghai Municipal Education Commission-Gaofeng Clinical Medicine Grant Support (20161313 to GZ), Shanghai Natural Science Foundation (20ZR1433100 to XY), Shanghai Shenkang Hospital Development Center (SHDC2020CR3057B to XY; SHDC2020CR6009-002 to WD), Shanghai Municipal Key Clinical Specialty, Shanghai Collaborative Innovation Center for Translational Medicine (TM202004 to XY), Beijing Kuanghua foundation for the development of Chinese and Western Medicine (BKF) (KH-2021-LLZX-018 to XY; KH-2021-LLZX-049 to HL), Shanghai Jiao Tong University School of Medicine (YG2021GD02 and TMSK-2021-207 to XY), innovative research team of high-level local universities in Shanghai (SHSMU-ZLCX20210200 to GZ), and 111project (no. B21024 to GZ).

Author information

Author notes

  1. These authors contributed equally: Xiaoran Long, Huaiwu Lu, Mei-Chun Cai, Jingyu Zang.

Authors and Affiliations

  1. State Key Laboratory of Oncogenes and Related Genes, Department of Obstetrics and Gynecology, Shanghai Cancer Institute, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China

    Xiaoran Long, Mei-Chun Cai, Jingyu Zang, Zhuqing Zhang, Xiaoshi Liu, Lin Cheng, Wen Di, Guanglei Zhuang & Xia Yin

  2. Shanghai Key Laboratory of Gynecologic Oncology, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China

    Xiaoran Long, Zhuqing Zhang, Xiaoshi Liu, Lin Cheng, Wen Di, Guanglei Zhuang & Xia Yin

  3. Department of Gynecologic Oncology, Sun Yat-sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, China

    Huaiwu Lu

  4. Department of Pathology, The Affiliated Hospital of Qingdao University, Qingdao, China

    Jie Wu

  5. Department of Radiology, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China

    Jiejun Cheng

  6. School of Biomedical Sciences, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China

    Lydia W. T. Cheung

  7. Department of Obstetrics and Gynecology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China

    Zhen Shen & Ying Zhou

Authors
  1. Xiaoran Long
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Huaiwu Lu
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Mei-Chun Cai
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Jingyu Zang
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Zhuqing Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Jie Wu
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Xiaoshi Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Lin Cheng
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Jiejun Cheng
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Lydia W. T. Cheung
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Zhen Shen
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Ying Zhou
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Wen Di
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. Guanglei Zhuang
    View author publications

    You can also search for this author in PubMed Google Scholar

  15. Xia Yin
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

XY, GZ and WD designed and supervised the study. XL, HL, JZ, ZZ, JW, XL, LC, JC, LWTC, ZS and YZ performed the experiments and analysed the data. MCC developed the bioinformatics pipeline. GZ and XL wrote the manuscript. All authors read and approved the final version of the manuscript.

Corresponding authors

Correspondence to Wen Di, Guanglei Zhuang or Xia Yin.

Ethics declarations

Competing interests

The authors declare no competing interests.

Ethics approval and consent to participate

The study protocols were reviewed and approved by the institutional ethics committee of Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine (approval number: 2018-114). Written informed consent was obtained from all the patients.

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary information

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Long, X., Lu, H., Cai, MC. et al. APOBEC3B stratifies ovarian clear cell carcinoma with distinct immunophenotype and prognosis. Br J Cancer 128, 2054–2062 (2023). https://doi.org/10.1038/s41416-023-02239-5

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41416-023-02239-5

Search

Advanced search

Quick links