{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T07:06:17Z","timestamp":1789369577594,"version":"build-2803163510"},"reference-count":36,"publisher":"National Academy of Sciences","issue":"50","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2010,12,14]]},"abstract":"<jats:p>\n                    High hyperdiploid acute lymphoblastic leukemia (ALL) is one of the most common malignancies in children. It is characterized by gain of chromosomes, typically +X, +4, +6, +10, +14, +17, +18, and +21,+21; little is known about additional genetic aberrations. Approximately 20% of the patients relapse; therefore it is clinically important to identify risk-stratifying markers. We used SNP array analysis to investigate a consecutive series of 74 cases of high hyperdiploid ALL. We show that the characteristic chromosomal gains are even more frequent than previously believed, indicating that karyotyping mistakes are common, and that almost 80% of the cases display additional abnormalities detectable by SNP array analysis. Subclonality analysis strongly implied that the numerical aberrations were primary and arose before structural events, suggesting that step-wise evolution of the leukemic clone is common. An association between duplication of 1q and +5 was seen (\n                    <jats:italic>P<\/jats:italic>\n                    = 0.003). Other frequent abnormalities included whole-chromosome uniparental isodisomies (wUPIDs) 9 and 11, gain of 17q not associated with isochromosome formation, extra gain of part of 21q, deletions of ETS variant 6 (\n                    <jats:italic>ETV6<\/jats:italic>\n                    ), cyclin-dependent kinase inhibitor 2A (\n                    <jats:italic>CKDN2A<\/jats:italic>\n                    ) and paired box 5 (\n                    <jats:italic>PAX5<\/jats:italic>\n                    ), and PAN3 poly(A) specific ribonuclease subunit homolog (\n                    <jats:italic>PAN3<\/jats:italic>\n                    ) microdeletions. Comparison of whole-chromosome and partial UPID9 suggested different pathogenetic outcomes, with the former not involving\n                    <jats:italic>CDKN2A<\/jats:italic>\n                    . Finally, two cases had partial deletions of AT rich interactive domain 5B (ARID5B), indicating that acquired as well as constitutional variants in this locus may be associated with pediatric ALL. Here we provide a comprehensive characterization of the genetic landscape of high hyperdiploid childhood ALL, including the heterogeneous pattern of secondary genetic events.\n                  <\/jats:p>","DOI":"10.1073\/pnas.1006981107","type":"journal-article","created":{"date-parts":[[2010,11,23]],"date-time":"2010-11-23T00:41:46Z","timestamp":1290472906000},"page":"21719-21724","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":122,"title":["Genetic landscape of high hyperdiploid childhood acute lymphoblastic leukemia"],"prefix":"10.1073","volume":"107","author":[{"given":"Kajsa","family":"Paulsson","sequence":"first","affiliation":[{"name":"Department of Clinical Genetics, University and Regional Laboratories, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erik","family":"Forestier","sequence":"additional","affiliation":[{"name":"Department of Clinical Sciences, Pediatrics, University of Ume\u00e5, SE-901 85 Ume\u00e5, Sweden;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henrik","family":"Lilljebj\u00f6rn","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics, University and Regional Laboratories, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jesper","family":"Heldrup","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Sk\u00e5ne University Hospital, Lund University, SE-221 85 Lund, Sweden;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mikael","family":"Behrendtz","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Link\u00f6ping University Hospital, SE-581 85 Link\u00f6ping, Sweden; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bryan D.","family":"Young","sequence":"additional","affiliation":[{"name":"Institute of Cancer, Barts and the Royal London School of Medicine, London EC1M 6BQ, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bertil","family":"Johansson","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics, University and Regional Laboratories, and"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2010,11,22]]},"reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.1093\/jnci\/djg064"},{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1002\/gcc.20671"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/0165-4608(81)90076-5"},{"key":"e_1_3_3_4_2","first-page":"10","article-title":"Collaborative study of karyotypes in childhood acute lymphoblastic leukemias","volume":"7","author":"Groupe Francais de Cytog\u00e9n\u00e9tique H\u00e9matologique","year":"1993","unstructured":"; Groupe Francais de Cytog\u00e9n\u00e9tique H\u00e9matologique, Collaborative study of karyotypes in childhood acute lymphoblastic leukemias. Leukemia 7, 10\u201319 (1993).","journal-title":"Leukemia"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2003-04-1128"},{"key":"e_1_3_3_6_2","first-page":"213","article-title":"Heterogeneity of hyperdiploid (51-67) childhood acute lymphoblastic leukemia","volume":"10","author":"Raimondi SC","year":"1996","unstructured":"SC Raimondi, et al., Heterogeneity of hyperdiploid (51-67) childhood acute lymphoblastic leukemia. Leukemia 10, 213\u2013224 (1996).","journal-title":"Leukemia"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2141.2008.06980.x"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.leu.2403101"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1002\/gcc.20010"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2002-01-0144"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng.430"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng.432"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1002\/gcc.20451"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0506637102"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1002\/gcc.20085"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng.469"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1117679"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2006-01-024729"},{"key":"e_1_3_3_19_2","doi-asserted-by":"crossref","first-page":"734","DOI":"10.1038\/sj.leu.2403673","article-title":"High concordance from independent studies by the Children's Cancer Group (CCG) and Pediatric Oncology Group (POG) associating favorable prognosis with combined trisomies 4, 10, and 17 in children with NCI Standard-Risk B-precursor Acute Lymphoblastic Leukemia: A Children's Oncology Group (COG) initiative","volume":"19","author":"Sutcliffe MJ","year":"2005","unstructured":"MJ Sutcliffe, et al., High concordance from independent studies by the Children's Cancer Group (CCG) and Pediatric Oncology Group (POG) associating favorable prognosis with combined trisomies 4, 10, and 17 in children with NCI Standard-Risk B-precursor Acute Lymphoblastic Leukemia: A Children's Oncology Group (COG) initiative. Leukemia 19, 734\u2013740 (2005).","journal-title":"Leukemia"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng1416"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(10)70066-8"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature05610"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1002\/gcc.20222"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2007-05-088310"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature05690"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-05-2017"},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0800408105"},{"key":"e_1_3_3_28_2","doi-asserted-by":"publisher","DOI":"10.1101\/gr.6584707"},{"key":"e_1_3_3_29_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V73.7.1963.1963"},{"key":"e_1_3_3_30_2","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2000.18.9.1876"},{"key":"e_1_3_3_31_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0602360103"},{"key":"e_1_3_3_32_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2006-08-040436"},{"key":"e_1_3_3_33_2","doi-asserted-by":"publisher","DOI":"10.1038\/leu.2010.39"},{"key":"e_1_3_3_34_2","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.16.10.5744"},{"key":"e_1_3_3_35_2","doi-asserted-by":"publisher","DOI":"10.1101\/gr.168801"},{"key":"e_1_3_3_36_2","doi-asserted-by":"publisher","DOI":"10.1038\/leu.2009.251"}],"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.1006981107","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,4,12]],"date-time":"2022-04-12T20:08:15Z","timestamp":1649794095000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/full\/10.1073\/pnas.1006981107"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2010,11,22]]},"references-count":36,"journal-issue":{"issue":"50","published-print":{"date-parts":[[2010,12,14]]}},"alternative-id":["10.1073\/pnas.1006981107"],"URL":"https:\/\/doi.org\/10.1073\/pnas.1006981107","relation":{},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[2010,11,22]]},"assertion":[{"value":"2010-11-22","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}