diff --git a/content/manual-references.json b/content/manual-references.json
index 401ebd93..8eb2f5d7 100644
--- a/content/manual-references.json
+++ b/content/manual-references.json
@@ -3718,5 +3718,146 @@
"PMCID": "PMC3163565",
"PMID": "21816040",
"id": "doi:10.1186/1471-2105-12-323"
+ },
+ {
+ "publisher": "American Association for Cancer Research (AACR)",
+ "issue": "18",
+ "abstract": "Abstract\n \n Purpose:\n PNOC003 is a multicenter precision medicine trial for children and young adults with newly diagnosed diffuse intrinsic pontine glioma (DIPG).\n \n \n Patients and Methods:\n Patients (3–25 years) were enrolled on the basis of imaging consistent with DIPG. Biopsy tissue was collected for whole-exome and mRNA sequencing. After radiotherapy (RT), patients were assigned up to four FDA-approved drugs based on molecular tumor board recommendations. H3K27M-mutant circulating tumor DNA (ctDNA) was longitudinally measured. Tumor tissue and matched primary cell lines were characterized using whole-genome sequencing and DNA methylation profiling. When applicable, results were verified in an independent cohort from the Children's Brain Tumor Network (CBTN).\n \n \n Results:\n Of 38 patients enrolled, 28 patients (median 6 years, 10 females) were reviewed by the molecular tumor board. Of those, 19 followed treatment recommendations. Median overall survival (OS) was 13.1 months [95% confidence interval (CI), 11.2–18.4] with no difference between patients who followed recommendations and those who did not. H3K27M-mutant ctDNA was detected at baseline in 60% of cases tested and associated with response to RT and survival. Eleven cell lines were established, showing 100% fidelity of key somatic driver gene alterations in the primary tumor. In H3K27-altered DIPGs, TP53 mutations were associated with worse OS (TP53mut 11.1 mo; 95% CI, 8.7–14; TP53wt 13.3 mo; 95% CI, 11.8–NA; P = 3.4e−2), genome instability (P = 3.1e−3), and RT resistance (P = 6.4e−4). The CBTN cohort confirmed an association between TP53 mutation status, genome instability, and clinical outcome.\n \n \n Conclusions:\n Upfront treatment-naïve biopsy provides insight into clinically relevant molecular alterations and prognostic biomarkers for H3K27-altered DIPGs.\n ",
+ "DOI": "10.1158/1078-0432.ccr-22-0803",
+ "type": "article-journal",
+ "page": "3965-3978",
+ "source": "Crossref",
+ "title": "Upfront Biology-Guided Therapy in Diffuse Intrinsic Pontine Glioma: Therapeutic, Molecular, and Biomarker Outcomes from PNOC003",
+ "volume": "28",
+ "author": [
+ {
+ "given": "Cassie",
+ "family": "Kline"
+ },
+ {
+ "given": "Payal",
+ "family": "Jain"
+ },
+ {
+ "given": "Lindsay",
+ "family": "Kilburn"
+ },
+ {
+ "given": "Erin R.",
+ "family": "Bonner"
+ },
+ {
+ "given": "Nalin",
+ "family": "Gupta"
+ },
+ {
+ "given": "John R.",
+ "family": "Crawford"
+ },
+ {
+ "given": "Anu",
+ "family": "Banerjee"
+ },
+ {
+ "given": "Roger J.",
+ "family": "Packer"
+ },
+ {
+ "given": "Javier",
+ "family": "Villanueva-Meyer"
+ },
+ {
+ "given": "Tracy",
+ "family": "Luks"
+ },
+ {
+ "given": "Yalan",
+ "family": "Zhang"
+ },
+ {
+ "given": "Madhuri",
+ "family": "Kambhampati"
+ },
+ {
+ "given": "Jie",
+ "family": "Zhang"
+ },
+ {
+ "given": "Sridevi",
+ "family": "Yadavilli"
+ },
+ {
+ "given": "Bo",
+ "family": "Zhang"
+ },
+ {
+ "given": "Krutika S.",
+ "family": "Gaonkar"
+ },
+ {
+ "given": "Jo Lynne",
+ "family": "Rokita"
+ },
+ {
+ "given": "Adam",
+ "family": "Kraya"
+ },
+ {
+ "given": "John",
+ "family": "Kuhn"
+ },
+ {
+ "given": "Winnie",
+ "family": "Liang"
+ },
+ {
+ "given": "Sara",
+ "family": "Byron"
+ },
+ {
+ "given": "Michael",
+ "family": "Berens"
+ },
+ {
+ "given": "Annette",
+ "family": "Molinaro"
+ },
+ {
+ "given": "Michael",
+ "family": "Prados"
+ },
+ {
+ "given": "Adam",
+ "family": "Resnick"
+ },
+ {
+ "given": "Sebastian M.",
+ "family": "Waszak"
+ },
+ {
+ "given": "Javad",
+ "family": "Nazarian"
+ },
+ {
+ "given": "Sabine",
+ "family": "Mueller"
+ }
+ ],
+ "container-title": "Clinical Cancer Research",
+ "container-title-short": "Clin Cancer Res",
+ "language": "en",
+ "issued": {
+ "date-parts": [
+ [
+ 2022,
+ 7,
+ 19
+ ]
+ ]
+ },
+ "URL": "https://doi.org/gqh9gb",
+ "PMCID": "PMC9475246",
+ "PMID": "35852795",
+ "id": "doi:10.1158/1078-0432.ccr-22-0803"
}
]