Stratified Medicine Pediatrics: Cell-Free DNA and Serial Tumor Sequencing Identifies Subtype-Specific Cancer Evolution and Epigenetic States.

George, SL.; Lynn, C.; Stankunaite, R.; Hughes, D.; Sauer, CM.; Chalker, J.; Waqar Ahmed, S.; Oostveen, M.; Proszek, PZ.; Yuan, L.; Shaikh, R.; Jamal, S.; Brew, A.; Tall, J.; Rogers, T.; Clifford, SC.; Vormoor, J.; Shipley, JM.; Tweddle, DA.; Jones, C.; Willis, C.; Burke, GAA.; Vedi, A.; Howell, L.; Johnston, R.; Rees, H.; Adams, M.; Jesudason, A.; Ronghe, M.; Elliott, M.; Ross, E.; Makin, G.; Campbell-Hewson, Q.; Grundy, RG.; Turnbull, J.; Wilson, S.; Lee, V.; Gray, JC.; Stoneham, S.; Gatz, SA.; Marshall, LV.; Angelini, P.; Anderson, J.; Cresswell, GD.; Graham, TA.; Al-Lazikani, B.; Cortes-Ciriano, I.; Kearns, P.; Hutchinson, JC.; Hargrave, D.; Jacques, TS.; Hubank, M.; Sottoriva, A.; Chesler, L.

Stratified Medicine Pediatrics: Cell-Free DNA and Serial Tumor Sequencing Identifies Subtype-Specific Cancer Evolution and Epigenetic States.

All Authors

George, SL.

Lynn, C.

Stankunaite, R.

Hughes, D.

Sauer, CM.

Chalker, J.

Waqar Ahmed, S.

Oostveen, M.

Proszek, PZ.

Yuan, L.

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LTHT Author

Elliott, Martin

LTHT Department

Leeds Children's Hospital
Children & Teenage Oncology & Haematology

Publication Date

2025

Item Type

Journal Article

Abstract

SIGNIFICANCE: In tumors of childhood, we identify mutations in epigenetic genes as drivers of relapse, with matched cfDNA sequencing showing significant intratumor genetic heterogeneity and cell-state specific patterns of chromatin accessibility. This highlights the power of cfDNA analysis to identify both genetic and epigenetic drivers of aggressive disease in pediatric cancers.