Supplementary Materials

Supplementary Material for:

Therapeutic targeting of PGBD5-induced DNA repair dependency in pediatric solid tumors

Anton G. Henssen, Casie Reed, Eileen Jiang, Heathcliff Dorado Garcia, Jennifer von Stebut, Ian C. MacArthur, Patrick Hundsdoerfer, Jun Hyun Kim, Elisa de Stanchina, Yasumichi Kuwahara, Hajime Hosoi, Neil J. Ganem, Filemon Dela Cruz, Andrew L. Kung, Johannes H. Schulte, John H. Petrini, Alex Kentsis*

*Corresponding author. Email: kentsisresearchgroup{at}gmail.com

Published 1 November 2017, Sci. Transl. Med. 9, eaam9078 (2017)
DOI: 10.1126/scitranslmed.aam9078

This PDF file includes:

  • Materials and Methods
  • Fig. S1. Ligase 4–deficient MEFs exhibit impaired cell proliferation.
  • Fig. S2. PGBD5 expression is sufficient to confer sensitivity to ATM and ATR inhibitors.
  • Fig. S3. GFP-PGBD5 expression in RPE cells does not affect cell cycle kinetics.
  • Fig. S4. AZD6732 induces punctate γH2AX accumulation.
  • Fig. S5. Rhabdoid tumor, medulloblastoma, neuroblastoma, and Ewing sarcoma cells are sensitive to AZD6738.
  • Fig. S6. Expression of PGBD5 in tumor cell lines correlates with their susceptibility to AZD6738, unlike TP53 and MYC/N status.
  • Fig. S7. ATM is expressed in PGBD5-expressing normal and tumor cell lines.
  • Fig. S8. AZD6738 treatment leads to increased DNA DSB as evidenced by TUNEL.
  • Fig. S9. Neuroblastoma cell lines do not tolerate PGBD5 depletion.
  • Fig. S10. PGBD5 expression is necessary for tumor cell susceptibility to KU60019.
  • Fig. S11. AZD6738 treatment decreases pediatric xenograft tumor growth in mice.
  • Fig. S12. Mouse weights are not affected by treatment with AZD6738.
  • Fig. S13. VE822 treatment does not inhibit pediatric xenograft tumor growth in mice.
  • Fig. S14. PGBD5 induces a synthetic lethal DNA damage signaling dependency.
    Table S1. Selectivity profiles of inhibitors of DNA damage signaling.
  • Table S2. Mutational profiles of genes that affect susceptibility of cells to inhibitors of DNA damage signaling.
  • Table S3. Statistical analysis of drug susceptibility upon PGBD5 depletion.
  • Table S4. Demographic and molecular features of neuroblastoma patients.
  • Table S5. Oligonucleotide primers.
  • Table S6. Antibodies.
  • References (5869)

[Download PDF]