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Impaired Fanconi anemia pathway causes DNA hypomethylation in human angiosarcomas

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Abstract

Angiosarcomas (AS) is a rare soft tissue sarcomas with poor treatment options and a dismal prognosis. The abnormal DNA methylation pattern has been determined as the certain clinical relevance with different angiosarcoma subtypes. However, the profound mechanism is not clear. In present study, we studied thirty-six AS with or without chronic lymphedema, and reported that DNA damage was an important factor causing DNA methylation abnormality. Furthermore, we determined that the impaired Fanconi anemia (FA) pathway contributed to severe DNA damage in AS with chronic lymphedema. We also observed that the activated FANCD2 could facilitate DNMT1 recruitment on genomic DNA. Our study uncovers a novel regulatory mechanism of FA pathway on DNA methylation, and is a benefit to advanced understanding the pathogenesis of AS, as well as providing the potential therapeutic targets for AS treatment.

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Availability of data and materials

The datasets and supporting materials generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

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Funding

This project is supported by Natural Science Foundation of Henan Province (NO. 212300410390).

Author information

Authors and Affiliations

  1. Department of Laboratory, Henan Provincial People’s Hospital, NO. 7, Weiwu Road, Zhengzhou, 450003, Henan, China

    Kangning Zhu, Fengxia Guo & Lan Gao

  2. Department of Gastroenterology, Henan Provincial People’s Hospital, NO. 7, Weiwu Road, Zhengzhou, 450003, Henan, China

    Suofeng Sun

Authors
  1. Kangning Zhu
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  2. Suofeng Sun
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  3. Fengxia Guo
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  4. Lan Gao
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Contributions

Contributions: (I) conception and design: KNZ; (II) administrative support: KNZ; (III) provision of study materials or patients: KNZ; (IV) collection and assembly of data: SFS, FXG and LG; (V) data analysis and interpretation: KNZ; (VI) manuscript writing: KNZ; (VII) final approval of manuscript: all the authors.

Corresponding author

Correspondence to Kangning Zhu.

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Conflict of interest

The authors declare no conflict of interests.

Ethical approval

All the participants understood and signed the informed consent. Signed informed consent and ethics committee documents of Ethics Committee of People’s Hospital of Henan Province (HNPH: E2022-230) were all provided to approve this study.

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Supplementary Information

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13577_2022_736_MOESM1_ESM.tif

Supplementary figure 1. Characterization of AS and para-tumor primary cells of. Cell morphology of primary cells cultured in 3rd, 5th and 10th day (A). Primary AS cells identified by CD31 and CD34, red and blue peak represent the median fluorescence intensity of CD31 and CD34 in para-tumor and AS cells (B). Proportion of different cell cycle stages in AS and para-tumor primary cells by FACS assay (C). ASCL: angiosarcomas with chronic lymphedema; ASNCL: AS without chronic lymphedema; PT: para-tumor. Supplementary file1 (TIF 5311 KB)

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Supplementary file3 (DOCX 19 KB)

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Zhu, K., Sun, S., Guo, F. et al. Impaired Fanconi anemia pathway causes DNA hypomethylation in human angiosarcomas. Human Cell 35, 1602–1611 (2022). https://doi.org/10.1007/s13577-022-00736-y

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  • DOI: https://doi.org/10.1007/s13577-022-00736-y

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