{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,19]],"date-time":"2026-02-19T23:10:18Z","timestamp":1771542618559,"version":"3.50.1"},"reference-count":62,"publisher":"MDPI AG","issue":"22","license":[{"start":{"date-parts":[[2021,11,12]],"date-time":"2021-11-12T00:00:00Z","timestamp":1636675200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["BE6555\/1-1"],"award-info":[{"award-number":["BE6555\/1-1"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["BE6555\/2-1"],"award-info":[{"award-number":["BE6555\/2-1"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>B-cell precursor acute lymphoblastic leukemia (BCP-ALL) is the most common cancer in children, and significant progress has been made in diagnostics and the treatment of this disease based on the subtypes of BCP-ALL. However, in a large proportion of cases (B-other), recurrent BCP-ALL-associated genomic alterations remain unidentifiable by current diagnostic procedures. In this study, we performed RNA sequencing and analyzed gene fusions, expression profiles, and mutations in diagnostic samples of 185 children with BCP-ALL. Gene expression clustering showed that a subset of B-other samples partially clusters with some of the known subgroups, particularly DUX4-positive. Mutation analysis coupled with gene expression profiling revealed the presence of distinctive BCP-ALL subgroups, characterized by the presence of mutations in known ALL driver genes, e.g., PAX5 and IKZF1. Moreover, we identified novel fusion partners of lymphoid lineage transcriptional factors ETV6, IKZF1 and PAX5. In addition, we report on low blast count detection thresholds and show that the use of EDTA tubes for sample collection does not have adverse effects on sequencing and downstream analysis. Taken together, our findings demonstrate the applicability of whole-transcriptome sequencing for personalized diagnostics in pediatric ALL, including tentative classification of the B-other cases that are difficult to diagnose using conventional methods.<\/jats:p>","DOI":"10.3390\/cancers13225653","type":"journal-article","created":{"date-parts":[[2021,11,12]],"date-time":"2021-11-12T08:10:22Z","timestamp":1636704622000},"page":"5653","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Transcriptional and Mutational Profiling of B-Other Acute Lymphoblastic Leukemia for Improved Diagnostics"],"prefix":"10.3390","volume":"13","author":[{"given":"Philippe","family":"Chouvarine","sequence":"first","affiliation":[{"name":"Institute of Human Genetics, Hannover Medical School (MHH), 30625 Hannover, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9398-2637","authenticated-orcid":false,"given":"\u017deljko","family":"Anti\u0107","sequence":"additional","affiliation":[{"name":"Institute of Human Genetics, Hannover Medical School (MHH), 30625 Hannover, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jana","family":"Lentes","sequence":"additional","affiliation":[{"name":"Institute of Human Genetics, Hannover Medical School (MHH), 30625 Hannover, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Charlotte","family":"Schr\u00f6der","sequence":"additional","affiliation":[{"name":"Institute of Human Genetics, Hannover Medical School (MHH), 30625 Hannover, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Julia","family":"Alten","sequence":"additional","affiliation":[{"name":"Berlin-Frankfurt-M\u00fcnster ALL Study Group Germany (BFM-G), Department of Pediatrics, University Medical Center Schleswig-Holstein, Campus Kiel, 24105 Kiel, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Monika","family":"Br\u00fcggemann","sequence":"additional","affiliation":[{"name":"Department of Hematology, University Hospital Schleswig-Holstein, Campus Kiel, 24105 Kiel, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2310-2267","authenticated-orcid":false,"given":"Enrique","family":"Carrillo-de Santa Pau","sequence":"additional","affiliation":[{"name":"Computational Biology Group, Precision Nutrition and Cancer Research Program, IMDEA Food Institute, 28049 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thomas","family":"Illig","sequence":"additional","affiliation":[{"name":"Institute of Human Genetics, Hannover Medical School (MHH), 30625 Hannover, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Teresa","family":"Laguna","sequence":"additional","affiliation":[{"name":"Computational Biology Group, Precision Nutrition and Cancer Research Program, IMDEA Food Institute, 28049 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1070-0217","authenticated-orcid":false,"given":"Denis","family":"Schewe","sequence":"additional","affiliation":[{"name":"Berlin-Frankfurt-M\u00fcnster ALL Study Group Germany (BFM-G), Department of Pediatrics, University Medical Center Schleswig-Holstein, Campus Kiel, 24105 Kiel, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Martin","family":"Stanulla","sequence":"additional","affiliation":[{"name":"Pediatric Hematology and Oncology, Hannover Medical School (MHH), 30625 Hannover, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ming","family":"Tang","sequence":"additional","affiliation":[{"name":"Institute of Human Genetics, Hannover Medical School (MHH), 30625 Hannover, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Martin","family":"Zimmermann","sequence":"additional","affiliation":[{"name":"Pediatric Hematology and Oncology, Hannover Medical School (MHH), 30625 Hannover, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Martin","family":"Schrappe","sequence":"additional","affiliation":[{"name":"Department of Hematology, University Hospital Schleswig-Holstein, Campus Kiel, 24105 Kiel, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Brigitte","family":"Schlegelberger","sequence":"additional","affiliation":[{"name":"Institute of Human Genetics, Hannover Medical School (MHH), 30625 Hannover, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gunnar","family":"Cario","sequence":"additional","affiliation":[{"name":"Department of Hematology, University Hospital Schleswig-Holstein, Campus Kiel, 24105 Kiel, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anke K.","family":"Bergmann","sequence":"additional","affiliation":[{"name":"Institute of Human Genetics, Hannover Medical School (MHH), 30625 Hannover, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,11,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"495","DOI":"10.1001\/jamapediatrics.2015.4689","article-title":"Cancer in Adolescents and Young Adults: A Narrative Review of the Current Status and a View of the Future","volume":"170","author":"Barr","year":"2016","journal-title":"JAMA 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