@article{7cc924491bc54f84b40408f0528e4688,
title = "Implementation of DNA Methylation Array Profiling in Pediatric Central Nervous System Tumors: The AIM BRAIN Project: An Australian and New Zealand Children's Haematology/Oncology Group Study",
abstract = "DNA methylation array profiling for classifying pediatric central nervous system (CNS) tumors is a valuable adjunct to histopathology. However, unbiased prospective and interlaboratory validation studies have been lacking. The AIM BRAIN diagnostic trial involving 11 pediatric cancer centers in Australia and New Zealand was designed to test the feasibility of routine clinical testing and ran in parallel with the Molecular Neuropathology 2.0 (MNP2.0) study at Deutsches Krebsforschungszentrum (German Cancer Research Center). CNS tumors from 269 pediatric patients were prospectively tested on Illumina EPIC arrays, including 104 cases co-enrolled on MNP2.0. Using MNP classifier versions 11b4 and 12.5, we report classifications with a probability score ≥0.90 in 176 of 265 (66.4%) and 213 of 269 (79.2%) cases, respectively. Significant diagnostic information was obtained in 130 of 176 (74%) for 11b4, and 12 of 174 (7%) classifications were discordant with histopathology. Cases prospectively co-enrolled on MNP2.0 gave concordant classifications (99%) and score thresholds (93%), demonstrating excellent test reproducibility and sensitivity. Overall, DNA methylation profiling is a robust single workflow technique with an acceptable diagnostic yield that is considerably enhanced by the extensive subgroup and copy number profile information generated by the platform. The platform has excellent test reproducibility and sensitivity and contributes significantly to CNS tumor diagnosis.",
author = "White, {Christine L.} and Kinross, {Kathryn M.} and Moore, {Molly K.} and Elnaz Rasouli and Robyn Strong and Jones, {Janelle M.} and Cain, {Jason E.} and Dominik Sturm and Felix Sahm and Jones, {David T.W.} and Pfister, {Stefan M.} and Thomas Robertson and Colleen D'Arcy and Rodriguez, {Michael L.} and Dyke, {Jason M.} and Reimar Junckerstorff and Bhuva, {Dharmesh D.} and Davis, {Melissa J.} and Paul Wood and Tim Hassall and Ziegler, {David S.} and Stewart Kellie and Geoffrey McCowage and Frank Alvaro and Maria Kirby and Heath, {John A.} and Karen Tsui and Andrew Dodgshun and Eisenstat, {David D.} and Khuong-Quang, {Dong Anh} and Meaghan Wall and Algar, {Elizabeth M.} and Gottardo, {Nicholas G.} and Hansford, {Jordan R.}",
note = "Funding Information: AB was sponsored by the cooperative research group Australian and New Zealand Children's Haematology/Oncology Group. All 11 public hospital pediatric cancer centers throughout Australia and New Zealand were participating sites. Ethical approval was obtained from The Royal Children's Hospital Human Research Ethics Committee (reference number 17/RCHM/306), Tasmania Human Research Ethics Committee (reference number 20523), and New Zealand Central Health and Disability Ethics Committee (reference number 19/CEN/16). Participants were eligible if they had a suspected or confirmed primary brain or spinal cord tumor (at diagnosis or relapse); had an adequate sample; and were aged ≤21 years. Funding Information: Supported by Cancer Australia , the Robert Connor Dawes Foundation , and Carrie{\textquoteright}s Beanies 4 Brain Cancer Foundation . Institutional support provided through the Victorian Government{\textquoteright}s Operational Infrastructure Support Program . Funding Information: Supported by Cancer Australia, the Robert Connor Dawes Foundation, and Carrie's Beanies 4 Brain Cancer Foundation. Institutional support provided through the Victorian Government's Operational Infrastructure Support Program. Publisher Copyright: {\textcopyright} 2023 Association for Molecular Pathology and American Society for Investigative Pathology",
year = "2023",
month = oct,
doi = "10.1016/j.jmoldx.2023.06.013",
language = "English",
volume = "25",
pages = "709--728",
journal = "Journal of Molecular Diagnostics",
issn = "1525-1578",
publisher = "Association of Molecular Pathology",
number = "10",
}
