From Pediatric to Adult Brain Cancer: Exploring Histone H3 Mutations in Australian Brain Cancer Patients
Benedicte Grebstad Tune,
Heena Sareen,
Branka Powter,
Smadar Kahana-Edwin,
Adam Cooper,
Eng-Siew Koh,
Cheok S. Lee,
Joseph W. Po,
Geoff McCowage,
Mark Dexter,
Lucy Cain,
Geraldine O’Neill,
Victoria Prior,
Jonathan Karpelowsky,
Maria Tsoli,
Lars O. Baumbusch,
David Ziegler,
Tara L. Roberts,
Paul DeSouza,
Therese M. Becker,
Yafeng Ma
Affiliations
Benedicte Grebstad Tune
Department of Pediatric Research, Division of Paediatric and Adolescent Medicine, Oslo University Hospital Rikshospitalet, 0372 Oslo, Norway
Heena Sareen
Centre for Circulating Tumour Cell Diagnostics and Research, Ingham Institute for Applied Medical Research, 1 Campbell St, Liverpool, NSW 2170, Australia
Branka Powter
Centre for Circulating Tumour Cell Diagnostics and Research, Ingham Institute for Applied Medical Research, 1 Campbell St, Liverpool, NSW 2170, Australia
Smadar Kahana-Edwin
Children’s Cancer Research Unit, Kids Research, The Children’s Hospital at Westmead, Westmead, NSW 2145, Australia
Adam Cooper
Centre for Circulating Tumour Cell Diagnostics and Research, Ingham Institute for Applied Medical Research, 1 Campbell St, Liverpool, NSW 2170, Australia
Eng-Siew Koh
South Western Sydney Clinical School, University of New South Wales, Goulburn St, Liverpool, NSW 2170, Australia
Cheok S. Lee
School of Medicine, Western Sydney University, Campbelltown, NSW 2560, Australia
Joseph W. Po
Centre for Circulating Tumour Cell Diagnostics and Research, Ingham Institute for Applied Medical Research, 1 Campbell St, Liverpool, NSW 2170, Australia
Geoff McCowage
Cancer Centre for Children, The Children Hospital at Westmead, Westmead, NSW 2145, Australia
Mark Dexter
Neurosurgery, The Children Hospital at Westmead, Westmead, NSW 2145, Australia
Lucy Cain
Cancer Centre for Children, The Children Hospital at Westmead, Westmead, NSW 2145, Australia
Geraldine O’Neill
Children’s Cancer Research Unit, Kids Research, The Children’s Hospital at Westmead, Westmead, NSW 2145, Australia
Victoria Prior
Children’s Cancer Research Unit, Kids Research, The Children’s Hospital at Westmead, Westmead, NSW 2145, Australia
Jonathan Karpelowsky
Children’s Cancer Research Unit, Kids Research, The Children’s Hospital at Westmead, Westmead, NSW 2145, Australia
Maria Tsoli
Children’s Cancer Institute, Randwick, NSW 2031, Australia
Lars O. Baumbusch
Department of Pediatric Research, Division of Paediatric and Adolescent Medicine, Oslo University Hospital Rikshospitalet, 0372 Oslo, Norway
David Ziegler
Children’s Cancer Institute, Randwick, NSW 2031, Australia
Tara L. Roberts
Centre for Circulating Tumour Cell Diagnostics and Research, Ingham Institute for Applied Medical Research, 1 Campbell St, Liverpool, NSW 2170, Australia
Paul DeSouza
Centre for Circulating Tumour Cell Diagnostics and Research, Ingham Institute for Applied Medical Research, 1 Campbell St, Liverpool, NSW 2170, Australia
Therese M. Becker
Centre for Circulating Tumour Cell Diagnostics and Research, Ingham Institute for Applied Medical Research, 1 Campbell St, Liverpool, NSW 2170, Australia
Yafeng Ma
Centre for Circulating Tumour Cell Diagnostics and Research, Ingham Institute for Applied Medical Research, 1 Campbell St, Liverpool, NSW 2170, Australia
Genetic histone variants have been implicated in cancer development and progression. Mutations affecting the histone 3 (H3) family, H3.1 (encoded by HIST1H3B and HIST1H3C) and H3.3 (encoded by H3F3A), are mainly associated with pediatric brain cancers. While considered poor prognostic brain cancer biomarkers in children, more recent studies have reported H3 alterations in adult brain cancer as well. Here, we established reliable droplet digital PCR based assays to detect three histone mutations (H3.3-K27M, H3.3-G34R, and H3.1-K27M) primarily linked to childhood brain cancer. We demonstrate the utility of our assays for sensitively detecting these mutations in cell-free DNA released from cultured diffuse intrinsic pontine glioma (DIPG) cells and in the cerebral spinal fluid of a pediatric patient with DIPG. We further screened tumor tissue DNA from 89 adult patients with glioma and 1 with diffuse hemispheric glioma from Southwestern Sydney, Australia, an ethnically diverse region, for these three mutations. No histone mutations were detected in adult glioma tissue, while H3.3-G34R presence was confirmed in the diffuse hemispheric glioma patient.
