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It is important in pediatric and adolescent and young adult (AYA) malignancies, a group of rare cancers that are difficult to diagnose and progress quickly. We evaluated the usefulness of in\u2010hospital molecular profiling using a specific sequencing panel for pediatric and AYA malignancies in clarifying the diagnosis, predicting the prognosis, and identifying therapeutic targets. We evaluated the Oncomine Childhood Cancer Research Assay (203 genes, 1700 fusions) and analyzed 153 samples at diagnosis and 34 samples at relapse or refractory from 165 pediatric and AYA patients with various solid malignancies, including neuroblastoma, hepatoblastoma, brain tumor, and sarcoma. We simulated in\u2010hospital molecular profiling. In total, 320 reportable variants were identified in 153 samples (81.8%). Variants with clinical significance were identified in 62 samples (33.1%), including diagnostic variants in 26 (13.9%), prognostic variants in 17 (9%), targetable variants in 41 (21.9%), and variants with drug resistance in 18 (9.6%). Additionally, 62.0% and 94.1% of identified diagnostic and prognostic variants, respectively, had high levels of evidence. In five patients with cancer predisposition syndromes, all pathogenic germline mutations were validated. The turnaround time (TAT) from sample collection to reporting of the molecular profile was within seven working days. In\u2010hospital molecular profiling using a sequencing panel specified tailored for pediatric and AYA malignancies has a high rate of identifying reportable variants and enables accurate diagnosis, malignancy grading, and treatment selection, as well as cancer predisposition syndromes with a short TAT.<\/jats:p>","DOI":"10.1111\/cas.70312","type":"journal-article","created":{"date-parts":[[2025,12,29]],"date-time":"2025-12-29T07:27:16Z","timestamp":1766993236000},"page":"797-806","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Precision Oncology for Pediatric Solid Tumors Using In\u2010Hospital Pediatric\/\n                    <scp>AYA<\/scp>\n                    Malignancy\u2010Specific Panel Sequencing"],"prefix":"10.1111","volume":"117","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7783-0289","authenticated-orcid":false,"given":"Masato","family":"Kojima","sequence":"first","affiliation":[{"name":"Department of Pediatric Surgery Hiroshima University Hospital  Hiroshima Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7021-4707","authenticated-orcid":false,"given":"Sho","family":"Kurihara","sequence":"additional","affiliation":[{"name":"Department of Pediatric Surgery Hiroshima University Hospital  Hiroshima Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2861-0225","authenticated-orcid":false,"given":"Isamu","family":"Saeki","sequence":"additional","affiliation":[{"name":"Department of Pediatric Surgery Hiroshima University Hospital  Hiroshima Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-0578-8059","authenticated-orcid":false,"given":"Ryo","family":"Touge","sequence":"additional","affiliation":[{"name":"Department of Pediatric Surgery Hiroshima University Hospital  Hiroshima Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Keigo","family":"Nakashima","sequence":"additional","affiliation":[{"name":"Department of Pediatric Surgery Hiroshima University Hospital  Hiroshima Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1853-4759","authenticated-orcid":false,"given":"Shuhei","family":"Karakawa","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Hiroshima University Hospital  Hiroshima 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