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Understanding the biology of disease in this age group and the genetic basis of relapse is a key goal as patients with relapsed\/refractory disease have poor outcomes with conventional chemotherapy and novel molecular targets are required. This study examines the question of whether TYA T\u2010ALL has a specific biological\u2010molecular profile distinct from pediatric or adult T\u2010ALL.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Genomic characterization was undertaken of a retrospective discovery cohort of 80 patients aged 15\u201326 years with primary or relapsed T\u2010ALL, using a combination of Genome\u2010Wide Human SNP Array 6.0, targeted gene mutation and promoter methylation analyses. Findings were confirmed by MLPA, real\u2010time quantitative PCR, and FISH. Whole Exome Sequencing was performed in 4 patients with matched presentation and relapse to model clonal evolution. A prevalence analysis was performed on a final data set of 1,792 individual cases to identify genetic lesions with age specific frequency patterns, including 972 pediatric (1\u201314 years), 439 TYA (15\u201324 years) and 381 adult (\u226525 years) cases. These cases were extracted from 19 publications with comparable genomic data identified through a PubMed search.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Genomic characterization of this large cohort of TYA T\u2010ALL patients identified recurrent isochromosome 7q i(7q) in our discovery cohort (n = 3). Prevalence analysis did not identify any age specific genetic abnormalities. Genomic analysis of 6 pairs of matched presentation \u2013 relapsed T\u2010ALL established that all relapses were clonally related to the initial leukemia. Whole exome sequencing analysis revealed recurrent, targetable, mutations disrupting NOTCH, PI3K\/AKT\/mTOR, FLT3, NRAS as well as drug metabolism pathways.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>All genetic aberrations in TYA T\u2010ALL occurred with an incidence similar or intermediate to that reported in the pediatric and adult literature, demonstrating that overall TYA T\u2010ALL exhibits a transitional genomic profile. Analysis of matched presentation \u2013 relapse supported the hypothesis that relapse is driven by the Darwinian evolution of sub\u2010clones associated with drug resistance (NT5C2 and TP53 mutations) and re\u2010iterative mutation of known key T\u2010ALL drivers, including NOTCH1.<\/jats:p><\/jats:sec>","DOI":"10.1002\/cam4.4024","type":"journal-article","created":{"date-parts":[[2021,6,4]],"date-time":"2021-06-04T08:44:03Z","timestamp":1622796243000},"page":"4864-4873","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["The genomic landscape of teenage and young adult T\u2010cell acute lymphoblastic leukemia"],"prefix":"10.1002","volume":"10","author":[{"given":"Marcela B.","family":"Mansur","sequence":"first","affiliation":[{"name":"Centre for Evolution and Cancer The Institute of Cancer Research London UK"},{"name":"Paediatric Haematology\u2010Oncology Program, Research Centre Instituto Nacional de C\u00e2ncer Rio 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