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The ongoing international clinical trial<jats:italic>LBL2018<\/jats:italic>(NCT04043494) represents an ideal opportunity to implement a common analytic approach. Targeted next\u2010generation sequencing is well\u2010suited for this purpose; however, selection of relevant target genes for T\u2010LBL remains subject of ongoing debates. Our group has recently designed and evaluated a first target panel of 80 candidate genes for T\u2010LBL. The present study aimed at developing a novel optimized gene panel for large\u2010scale application and to promote an international agreement on a common core panel. Small sequence variants obtained from our former study were systematically analyzed and classified with regards to pathogenic relevance, to prioritize candidate genes. Additional genes were curated from literature and online databases for a more comprehensive analysis of relevant functions and signaling pathways. The new target panel<jats:italic>TGP\u2010T\u2010LBL<\/jats:italic>entails 84 candidate genes which are key actors in NOTCH, PI3K\u2010AKT, JAK\u2013STAT, RAS signaling, epigenetic regulation, transcription, DNA repair, cell cycle regulation, and ribosomal function. From our former gene panel, 35 out of 80 candidate genes were selected for the novel panel. Forty\u2010six out of 84 genes are currently being analyzed in the ongoing international trial LBL2018. Exploratory analysis of prognostic relevance on mutation\u2010level suggested a potential association of<jats:italic>PIK3CA<\/jats:italic>variants c.1624G&gt;A(p.Glu542Lys) and c.1633G&gt;A(p.Glu545Lys) to occurrence of relapse, emphasizing particular relevance of mutation analysis in PI3K\u2010AKT signaling. Our approach promotes comprehensive and clinically relevant mutational profiling of pediatric T\u2010LBL.<\/jats:p>","DOI":"10.1002\/gcc.23037","type":"journal-article","created":{"date-parts":[[2022,3,12]],"date-time":"2022-03-12T11:14:42Z","timestamp":1647083682000},"page":"459-470","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Design of a targeted next\u2010generation DNA sequencing panel for pediatric T\u2010cell lymphoblastic lymphoma to unravel biology and optimize treatment"],"prefix":"10.1002","volume":"61","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6356-5936","authenticated-orcid":false,"given":"Charlotte","family":"Ruether","sequence":"first","affiliation":[{"name":"Pediatric Hematology and Oncology University Hospital Muenster Muenster 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