Characterizing DNA methylation signatures of retinoblastoma using aqueous humor liquid biopsy

Hong-Tao Li; Liya Xu; Daniel J Weisenberger; Meng Li; Wanding Zhou; Chen-Ching Peng; Kevin Stachelek; David Cobrinik; Gangning Liang; Jesse L Berry

doi:10.1038/s41467-022-33248-2

Characterizing DNA methylation signatures of retinoblastoma using aqueous humor liquid biopsy

Nat Commun. 2022 Sep 21;13(1):5523. doi: 10.1038/s41467-022-33248-2.

Authors

Hong-Tao Li^#¹, Liya Xu^#², Daniel J Weisenberger^{3

4}, Meng Li⁵, Wanding Zhou⁶, Chen-Ching Peng², Kevin Stachelek², David Cobrinik^{2

3

4

7}, Gangning Liang^{8

9}, Jesse L Berry^{10

11

12}

Affiliations

¹ Department of Urology, University of Southern California, Norris Comprehensive Cancer Center, Los Angeles, CA, 90033, USA.
² Children's Hospital Los Angeles Vision Center & USC Roski Eye Institute, Keck School of Medicine, University of Southern California, Los Angeles, CA, 90027, USA.
³ Department of Biochemistry and Molecular Medicine, University of Southern California, Norris Comprehensive Cancer Center, Los Angeles, CA, 90033, USA.
⁴ Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA, 90033, USA.
⁵ Norris Medical Library, University of Southern California, Los Angeles, CA, 90033, USA.
⁶ University of Pennsylvania, Children's Hospital of Philadelphia, Philadelphia, PA, 19104, USA.
⁷ The Saban Research Institute, Children's Hospital Los Angeles, Los Angeles, CA, 90089, USA.
⁸ Department of Urology, University of Southern California, Norris Comprehensive Cancer Center, Los Angeles, CA, 90033, USA. gliang@usc.edu.
⁹ Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA, 90033, USA. gliang@usc.edu.
¹⁰ Children's Hospital Los Angeles Vision Center & USC Roski Eye Institute, Keck School of Medicine, University of Southern California, Los Angeles, CA, 90027, USA. jesse.berry@med.usc.edu.
¹¹ Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA, 90033, USA. jesse.berry@med.usc.edu.
¹² The Saban Research Institute, Children's Hospital Los Angeles, Los Angeles, CA, 90089, USA. jesse.berry@med.usc.edu.

^# Contributed equally.

Abstract

Retinoblastoma (RB) is a cancer that forms in the developing retina of babies and toddlers. The goal of therapy is to cure the tumor, save the eye and maximize vision. However, it is difficult to predict which eyes are likely to respond to therapy. Predictive molecular biomarkers are needed to guide prognosis and optimize treatment decisions. Direct tumor biopsy is not an option for this cancer; however, the aqueous humor (AH) is an alternate source of tumor-derived cell-free DNA (cfDNA). Here we show that DNA methylation profiling of the AH is a valid method to identify the methylation status of RB tumors. We identify 294 genes directly regulated by methylation that are implicated in p53 tumor suppressor (RB1, p53, p21, and p16) and oncogenic (E2F) pathways. Finally, we use AH to characterize molecular subtypes that can potentially be used to predict the likelihood of treatment success for retinoblastoma patients.

Publication types

Research Support, Non-U.S. Gov't
Research Support, N.I.H., Extramural

MeSH terms

Aqueous Humor / metabolism
Cell-Free Nucleic Acids* / metabolism
DNA Methylation / genetics
Humans
Infant
Liquid Biopsy
Retinal Neoplasms* / metabolism
Retinoblastoma* / pathology
Tumor Suppressor Protein p53 / genetics

Substances

Cell-Free Nucleic Acids
Tumor Suppressor Protein p53

Abstract

Publication types

MeSH terms

Substances

Grants and funding