{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T00:00:46Z","timestamp":1790380846615,"version":"4.1.0"},"reference-count":54,"publisher":"Springer Science and Business Media LLC","issue":"2","license":[{"start":{"date-parts":[[2017,2,3]],"date-time":"2017-02-03T00:00:00Z","timestamp":1486080000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2017,2,3]],"date-time":"2017-02-03T00:00:00Z","timestamp":1486080000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Blood Cancer Journal"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>In the search for genes that define critical steps of relapse in pediatric T-cell acute lymphoblastic leukemia (T-ALL) and can serve as prognostic markers, we performed targeted sequencing of 313 leukemia-related genes in 214 patients: 67 samples collected at the time of relapse and 147 at initial diagnosis. As relapse-specific genetic events, we identified activating mutations in <jats:italic>NT5C2<\/jats:italic> (<jats:italic>P<\/jats:italic>=0.0001, Fisher\u2019s exact test), inactivation of <jats:italic>TP53<\/jats:italic> (<jats:italic>P<\/jats:italic>=0.0007, Fisher\u2019s exact test) and duplication of chr17:q11.2-24.3 (<jats:italic>P<\/jats:italic>=0.0068, Fisher\u2019s exact test) in 32\/67 of T-ALL relapse samples. Alterations of <jats:italic>TP53<\/jats:italic> were frequently homozygous events, which significantly correlated with higher rates of copy number alterations in other genes compared with wild-type <jats:italic>TP53<\/jats:italic> (<jats:italic>P<\/jats:italic>=0.0004, Mann\u2013Whitney\u2019s test). We subsequently focused on mutations with prognostic impact and identified genes governing DNA integrity (<jats:italic>TP53<\/jats:italic>, <jats:italic>n<\/jats:italic>=8; <jats:italic>USP7<\/jats:italic>, <jats:italic>n<\/jats:italic>=4; <jats:italic>MSH6<\/jats:italic>, <jats:italic>n<\/jats:italic>=4), having key roles in the RAS signaling pathway (<jats:italic>KRAS<\/jats:italic>, <jats:italic>NRAS<\/jats:italic>, <jats:italic>n<\/jats:italic>=8), as well as <jats:italic>IL7R<\/jats:italic> (<jats:italic>n<\/jats:italic>=4) and <jats:italic>CNOT3<\/jats:italic> (<jats:italic>n<\/jats:italic>=4) to be exclusively mutated in fatal relapses. These markers recognize 24\/49 patients with a second event. In 17 of these patients with mostly refractory relapse and dire need for efficient treatment, we identified candidate targets for personalized therapy with p53 reactivating compounds, MEK inhibitors or JAK\/STAT-inhibitors that may be incorporated in future treatment strategies.<\/jats:p>","DOI":"10.1038\/bcj.2017.3","type":"journal-article","created":{"date-parts":[[2017,2,3]],"date-time":"2017-02-03T14:23:21Z","timestamp":1486131801000},"page":"e523-e523","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":89,"title":["Identification of a genetically defined ultra-high-risk group in relapsed pediatric T-lymphoblastic leukemia"],"prefix":"10.1038","volume":"7","author":[{"given":"P","family":"Richter-Pecha\u0144ska","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J B","family":"Kunz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J","family":"Hof","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M","family":"Zimmermann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5773-5620","authenticated-orcid":false,"given":"T","family":"Rausch","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"O R","family":"Bandapalli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"E","family":"Orlova","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G","family":"Scapinello","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J C","family":"Sagi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M","family":"Stanulla","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M","family":"Schrappe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G","family":"Cario","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6335-3274","authenticated-orcid":false,"given":"R","family":"Kirschner-Schwabe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C","family":"Eckert","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0352-2547","authenticated-orcid":false,"given":"V","family":"Benes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J O","family":"Korbel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M U","family":"Muckenthaler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A E","family":"Kulozik","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2017,2,3]]},"reference":[{"key":"BFbcj20173_CR1","doi-asserted-by":"publisher","first-page":"2077","DOI":"10.1182\/blood-2011-03-338707","volume":"118","author":"M Schrappe","year":"2011","unstructured":"Schrappe M, Valsecchi MG, Bartram CR, Schrauder A, Panzer-Grumayer R, Moricke A et al. Late MRD response determines relapse risk overall and in subsets of childhood T-cell ALL: results of the AIEOP-BFM-ALL 2000 study. Blood 2011; 118: 2077\u20132084.","journal-title":"Blood"},{"key":"BFbcj20173_CR2","unstructured":"von Stackelberg A. Charit\u00e9 Universit\u00e4tsmedizin Berlin, 2015, with reference to the trials ALL-REZ BFM 83 - 2002."},{"key":"BFbcj20173_CR3","doi-asserted-by":"publisher","first-page":"2807","DOI":"10.1182\/blood-2012-02-265884","volume":"120","author":"F Locatelli","year":"2012","unstructured":"Locatelli F, Schrappe M, Bernardo ME, Rutella S . How I treat relapsed childhood acute lymphoblastic leukemia. Blood 2012; 120: 2807\u20132816.","journal-title":"Blood"},{"key":"BFbcj20173_CR4","doi-asserted-by":"publisher","first-page":"S73","DOI":"10.1055\/s-0033-1337967","volume":"225","author":"G Henze","year":"2013","unstructured":"Henze G, von Stackelberg A, Eckert C . ALL-REZ BFM\u2014the consecutive trials for children with relapsed acute lymphoblastic leukemia. Klin Padiatr 2013; 225: S73\u2013S78.","journal-title":"Klin Padiatr"},{"key":"BFbcj20173_CR5","doi-asserted-by":"publisher","first-page":"2339","DOI":"10.1200\/JCO.2009.25.1983","volume":"28","author":"G Tallen","year":"2010","unstructured":"Tallen G, Ratei R, Mann G, Kaspers G, Niggli F, Karachunsky A et al. Long-term outcome in children with relapsed acute lymphoblastic leukemia after time-point and site-of-relapse stratification and intensified short-course multidrug chemotherapy: results of trial ALL-REZ BFM 90. J Clin Oncol 2010; 28: 2339\u20132347.","journal-title":"J Clin Oncol"},{"key":"BFbcj20173_CR6","doi-asserted-by":"publisher","first-page":"1442","DOI":"10.3324\/haematol.2015.129692","volume":"100","author":"JB Kunz","year":"2015","unstructured":"Kunz JB, Rausch T, Bandapalli OR, Eilers J, Pechanska P, Schuessele S et al. Pediatric T-lymphoblastic leukemia evolves into relapse by clonal selection, acquisition of mutations and promoter hypomethylation. Haematologica 2015; 100: 1442\u20131450.","journal-title":"Haematologica"},{"key":"BFbcj20173_CR7","doi-asserted-by":"publisher","first-page":"1377","DOI":"10.1126\/science.1164266","volume":"322","author":"CG Mullighan","year":"2008","unstructured":"Mullighan CG, Phillips LA, Su X, Ma J, Miller CB, Shurtleff SA et al. Genomic analysis of the clonal origins of relapsed acute lymphoblastic leukemia. Science 2008; 322: 1377\u20131380.","journal-title":"Science"},{"key":"BFbcj20173_CR8","doi-asserted-by":"publisher","first-page":"368","DOI":"10.1038\/nm.3078","volume":"19","author":"G Tzoneva","year":"2013","unstructured":"Tzoneva G, Perez-Garcia A, Carpenter Z, Khiabanian H, Tosello V, Allegretta M et al. Activating mutations in the NT5C2 nucleotidase gene drive chemotherapy resistance in relapsed ALL. Nat Med 2013; 19: 368\u2013371.","journal-title":"Nat Med"},{"key":"BFbcj20173_CR9","doi-asserted-by":"crossref","first-page":"3105","DOI":"10.1182\/blood.V84.9.3105.3105","volume":"84","author":"MB Diccianni","year":"1994","unstructured":"Diccianni MB, Yu J, Hsiao M, Mukherjee S, Shao LE, Yu AL . Clinical significance of p53 mutations in relapsed T-cell acute lymphoblastic leukemia. Blood 1994; 84: 3105\u20133112.","journal-title":"Blood"},{"key":"BFbcj20173_CR10","doi-asserted-by":"publisher","first-page":"3185","DOI":"10.1200\/JCO.2011.34.8144","volume":"29","author":"J Hof","year":"2011","unstructured":"Hof J, Krentz S, van Schewick C, Korner G, Shalapour S, Rhein P et al. Mutations and deletions of the TP53 gene predict nonresponse to treatment and poor outcome in first relapse of childhood acute lymphoblastic leukemia. J Clin Oncol 2011; 29: 3185\u20133193.","journal-title":"J Clin Oncol"},{"key":"BFbcj20173_CR11","doi-asserted-by":"publisher","first-page":"2023","DOI":"10.1038\/leu.2010.205","volume":"24","author":"E Clappier","year":"2010","unstructured":"Clappier E, Collette S, Grardel N, Girard S, Suarez L, Brunie G et al. NOTCH1 and FBXW7 mutations have a favorable impact on early response to treatment, but not on outcome, in children with T-cell acute lymphoblastic leukemia (T-ALL) treated on EORTC trials 58881 and 58951. Leukemia 2010; 24: 2023\u20132031.","journal-title":"Leukemia"},{"key":"BFbcj20173_CR12","doi-asserted-by":"publisher","first-page":"2003","DOI":"10.1038\/leu.2010.237","volume":"24","author":"A Ferrando","year":"2010","unstructured":"Ferrando A . NOTCH mutations as prognostic markers in T-ALL. Leukemia 2010; 24: 2003\u20132004.","journal-title":"Leukemia"},{"key":"BFbcj20173_CR13","doi-asserted-by":"publisher","first-page":"158","DOI":"10.3324\/haematol.2009.007526","volume":"95","author":"D Krieger","year":"2010","unstructured":"Krieger D, Moericke A, Oschlies I, Zimmermann M, Schrappe M, Reiter A et al. Frequency and clinical relevance of DNA microsatellite alterations of the CDKN2A\/B, ATM and p53 gene loci: a comparison between pediatric precursor T-cell lymphoblastic lymphoma and T-cell lymphoblastic leukemia. Haematologica 2010; 95: 158\u2013162.","journal-title":"Haematologica"},{"key":"BFbcj20173_CR14","doi-asserted-by":"publisher","first-page":"251","DOI":"10.1182\/blood-2014-02-558833","volume":"124","author":"A Stengel","year":"2014","unstructured":"Stengel A, Schnittger S, Weissmann S, Kuznia S, Kern W, Kohlmann A et al. TP53 mutations occur in 15.7% of ALL and are associated with MYC-rearrangement, low hypodiploidy, and a poor prognosis. Blood 2014; 124: 251\u2013258.","journal-title":"Blood"},{"key":"BFbcj20173_CR15","doi-asserted-by":"publisher","first-page":"74","DOI":"10.1182\/blood-2013-03-491092","volume":"122","author":"P Van Vlierberghe","year":"2013","unstructured":"Van Vlierberghe P, Ambesi-Impiombato A, De Keersmaecker K, Hadler M, Paietta E, Tallman MS et al. Prognostic relevance of integrated genetic profiling in adult T-cell acute lymphoblastic leukemia. Blood 2013; 122: 74\u201382.","journal-title":"Blood"},{"key":"BFbcj20173_CR16","doi-asserted-by":"publisher","first-page":"928","DOI":"10.3324\/haematol.2012.073585","volume":"98","author":"OR Bandapalli","year":"2013","unstructured":"Bandapalli OR, Zimmermann M, Kox C, Stanulla M, Schrappe M, Ludwig WD et al. NOTCH1 activation clinically antagonizes the unfavorable effect of PTEN inactivation in BFM-treated children with precursor T-cell acute lymphoblastic leukemia. Haematologica 2013; 98: 928\u2013936.","journal-title":"Haematologica"},{"key":"BFbcj20173_CR17","doi-asserted-by":"publisher","first-page":"1151","DOI":"10.1182\/blood-2005-12-4956","volume":"108","author":"S Breit","year":"2006","unstructured":"Breit S, Stanulla M, Flohr T, Schrappe M, Ludwig WD, Tolle G et al. Activating NOTCH1 mutations predict favorable early treatment response and long-term outcome in childhood precursor T-cell lymphoblastic leukemia. Blood 2006; 108: 1151\u20131157.","journal-title":"Blood"},{"key":"BFbcj20173_CR18","doi-asserted-by":"publisher","first-page":"2005","DOI":"10.1038\/leu.2010.203","volume":"24","author":"C Kox","year":"2010","unstructured":"Kox C, Zimmermann M, Stanulla M, Leible S, Schrappe M, Ludwig WD et al. The favorable effect of activating NOTCH1 receptor mutations on long-term outcome in T-ALL patients treated on the ALL-BFM 2000 protocol can be separated from FBXW7 loss of function. Leukemia 2010; 24: 2005\u20132013.","journal-title":"Leukemia"},{"key":"BFbcj20173_CR19","doi-asserted-by":"publisher","first-page":"941","DOI":"10.3324\/haematol.2015.139410","volume":"101","author":"V Gianfelici","year":"2016","unstructured":"Gianfelici V, Chiaretti S, Demeyer S, Di Giacomo F, Messina M, La Starza R et al. RNA sequencing unravels the genetics of refractory\/relapsed T-cell acute lymphoblastic leukemia. Prognostic and therapeutic implications. Haematologica 2016; 101: 941\u2013950.","journal-title":"Haematologica"},{"key":"BFbcj20173_CR20","doi-asserted-by":"publisher","first-page":"1405","DOI":"10.3324\/haematol.2011.059030","volume":"97","author":"L Zuurbier","year":"2012","unstructured":"Zuurbier L, Petricoin EF 3rd, Vuerhard MJ, Calvert V, Kooi C, Buijs-Gladdines JG et al. The significance of PTEN and AKT aberrations in pediatric T-cell acute lymphoblastic leukemia. Haematologica 2012; 97: 1405\u20131413.","journal-title":"Haematologica"},{"key":"BFbcj20173_CR21","doi-asserted-by":"publisher","first-page":"3398","DOI":"10.1172\/JCI61269","volume":"122","author":"P Van Vlierberghe","year":"2012","unstructured":"Van Vlierberghe P, Ferrando A . The molecular basis of T cell acute lymphoblastic leukemia. J Clin Invest 2012; 122: 3398\u20133406.","journal-title":"J Clin Invest"},{"key":"BFbcj20173_CR22","doi-asserted-by":"publisher","first-page":"e1003997","DOI":"10.1371\/journal.pgen.1003997","volume":"9","author":"ZK Atak","year":"2013","unstructured":"Atak ZK, Gianfelici V, Hulselmans G, De Keersmaecker K, Devasia AG, Geerdens E et al. Comprehensive analysis of transcriptome variation uncovers known and novel driver events in T-cell acute lymphoblastic leukemia. PLoS Genet 2013; 9: e1003997.","journal-title":"PLoS Genet"},{"key":"BFbcj20173_CR23","doi-asserted-by":"publisher","first-page":"186","DOI":"10.1038\/ng.2508","volume":"45","author":"K De Keersmaecker","year":"2013","unstructured":"De Keersmaecker K, Atak ZK, Li N, Vicente C, Patchett S, Girardi T et al. Exome sequencing identifies mutation in CNOT3 and ribosomal genes RPL5 and RPL10 in T-cell acute lymphoblastic leukemia. Nat Genet 2013; 45: 186\u2013190.","journal-title":"Nat Genet"},{"key":"BFbcj20173_CR24","doi-asserted-by":"publisher","first-page":"157","DOI":"10.1038\/nature10725","volume":"481","author":"J Zhang","year":"2012","unstructured":"Zhang J, Ding L, Holmfeldt L, Wu G, Heatley SL, Payne-Turner D et al. The genetic basis of early T-cell precursor acute lymphoblastic leukaemia. Nature 2012; 481: 157\u2013163.","journal-title":"Nature"},{"key":"BFbcj20173_CR25","doi-asserted-by":"publisher","first-page":"e188","DOI":"10.3324\/haematol.2014.104992","volume":"99","author":"OR Bandapalli","year":"2014","unstructured":"Bandapalli OR, Schuessele S, Kunz JB, Rausch T, Stutz AM, Tal N et al. The activating STAT5B N642H mutation is a common abnormality in pediatric T-cell acute lymphoblastic leukemia and confers a higher risk of relapse. Haematologica 2014; 99: e188\u2013e192.","journal-title":"Haematologica"},{"key":"BFbcj20173_CR26","doi-asserted-by":"publisher","first-page":"2283","DOI":"10.1093\/bioinformatics\/btp373","volume":"25","author":"DC Koboldt","year":"2009","unstructured":"Koboldt DC, Chen K, Wylie T, Larson DE, McLellan MD, Mardis ER et al. VarScan: variant detection in massively parallel sequencing of individual and pooled samples. Bioinformatics 2009; 25: 2283\u20132285.","journal-title":"Bioinformatics"},{"key":"BFbcj20173_CR27","unstructured":"R Core Team R A Language and Environment for Statistical Computing. R Foundation for Statistical Computing: Vienna, Austria, 2016."},{"key":"BFbcj20173_CR28","unstructured":"Grambsch TMTaPM Modeling Survival Data: Extending the Cox Model. Springer: New York, NY, USA, 2000."},{"key":"BFbcj20173_CR29","doi-asserted-by":"publisher","first-page":"214","DOI":"10.3324\/haematol.2014.113381","volume":"100","author":"N Bolli","year":"2015","unstructured":"Bolli N, Manes N, McKerrell T, Chi J, Park N, Gundem G et al. Characterization of gene mutations and copy number changes in acute myeloid leukemia using a rapid target enrichment protocol. Haematologica 2015; 100: 214\u2013222.","journal-title":"Haematologica"},{"key":"BFbcj20173_CR30","doi-asserted-by":"publisher","first-page":"1301","DOI":"10.3324\/haematol.2015.130179","volume":"100","author":"C Vicente","year":"2015","unstructured":"Vicente C, Schwab C, Broux M, Geerdens E, Degryse S, Demeyer S et al. Targeted sequencing identifies associations between IL7R-JAK mutations and epigenetic modulators in T-cell acute lymphoblastic leukemia. Haematologica 2015; 100: 1301\u20131310.","journal-title":"Haematologica"},{"key":"BFbcj20173_CR31","doi-asserted-by":"publisher","first-page":"61","DOI":"10.1016\/0027-5107(93)90052-H","volume":"285","author":"R Holliday","year":"1993","unstructured":"Holliday R, Grigg GW . DNA methylation and mutation. Mutat Res 1993; 285: 61\u201367.","journal-title":"Mutat Res"},{"key":"BFbcj20173_CR32","doi-asserted-by":"publisher","first-page":"1053","DOI":"10.1182\/blood-2008-10-186536","volume":"114","author":"M Remke","year":"2009","unstructured":"Remke M, Pfister S, Kox C, Toedt G, Becker N, Benner A et al. High-resolution genomic profiling of childhood T-ALL reveals frequent copy-number alterations affecting the TGF-beta and PI3K-AKT pathways and deletions at 6q15-16.1 as a genomic marker for unfavorable early treatment response. Blood 2009; 114: 1053\u20131062.","journal-title":"Blood"},{"key":"BFbcj20173_CR33","doi-asserted-by":"publisher","first-page":"338","DOI":"10.1038\/ng.542","volume":"42","author":"P Van Vlierberghe","year":"2010","unstructured":"Van Vlierberghe P, Palomero T, Khiabanian H, Van der Meulen J, Castillo M, Van Roy N et al. PHF6 mutations in T-cell acute lymphoblastic leukemia. Nat Genet 2010; 42: 338\u2013342.","journal-title":"Nat Genet"},{"key":"BFbcj20173_CR34","doi-asserted-by":"publisher","first-page":"494","DOI":"10.1038\/nrc.2016.63","volume":"16","author":"L Belver","year":"2016","unstructured":"Belver L, Ferrando A . The genetics and mechanisms of T cell acute lymphoblastic leukaemia. Nat Rev Cancer 2016; 16: 494\u2013507.","journal-title":"Nat Rev Cancer"},{"key":"BFbcj20173_CR35","doi-asserted-by":"publisher","first-page":"1546","DOI":"10.1126\/science.1235122","volume":"339","author":"B Vogelstein","year":"2013","unstructured":"Vogelstein B, Papadopoulos N, Velculescu VE, Zhou S, Diaz Jr LA, Kinzler KW . Cancer genome landscapes. Science 2013; 339: 1546\u20131558.","journal-title":"Science"},{"key":"BFbcj20173_CR36","doi-asserted-by":"publisher","first-page":"290","DOI":"10.1038\/ng.2558","volume":"45","author":"JA Meyer","year":"2013","unstructured":"Meyer JA, Wang J, Hogan LE, Yang JJ, Dandekar S, Patel JP et al. Relapse-specific mutations in NT5C2 in childhood acute lymphoblastic leukemia. Nat Genet 2013; 45: 290\u2013294.","journal-title":"Nat Genet"},{"key":"BFbcj20173_CR37","doi-asserted-by":"publisher","first-page":"1073","DOI":"10.1038\/nprot.2009.86","volume":"4","author":"P Kumar","year":"2009","unstructured":"Kumar P, Henikoff S, Ng PC . Predicting the effects of coding non-synonymous variants on protein function using the SIFT algorithm. Nat Protoc 2009; 4: 1073\u20131081.","journal-title":"Nat Protoc"},{"key":"BFbcj20173_CR38","doi-asserted-by":"publisher","first-page":"575","DOI":"10.1038\/nmeth0810-575","volume":"7","author":"JM Schwarz","year":"2010","unstructured":"Schwarz JM, Rodelsperger C, Schuelke M, Seelow D . MutationTaster evaluates disease-causing potential of sequence alterations. Nat Methods 2010; 7: 575\u2013576.","journal-title":"Nat Methods"},{"key":"BFbcj20173_CR39","doi-asserted-by":"publisher","first-page":"248","DOI":"10.1038\/nmeth0410-248","volume":"7","author":"IA Adzhubei","year":"2010","unstructured":"Adzhubei IA, Schmidt S, Peshkin L, Ramensky VE, Gerasimova A, Bork P et al. A method and server for predicting damaging missense mutations. Nat Methods 2010; 7: 248\u2013249.","journal-title":"Nat Methods"},{"key":"BFbcj20173_CR40","doi-asserted-by":"publisher","first-page":"701","DOI":"10.1038\/nrc2693","volume":"9","author":"R Brosh","year":"2009","unstructured":"Brosh R, Rotter V . When mutants gain new powers: news from the mutant p53 field. Nat Rev Cancer 2009; 9: 701\u2013713.","journal-title":"Nat Rev Cancer"},{"key":"BFbcj20173_CR41","doi-asserted-by":"publisher","first-page":"dju149","DOI":"10.1093\/jnci\/dju149","volume":"106","author":"EL Hedditch","year":"2014","unstructured":"Hedditch EL, Gao B, Russell AJ, Lu Y, Emmanuel C, Beesley J et al. ABCA transporter gene expression and poor outcome in epithelial ovarian cancer. J Natl Cancer Inst 2014; 106: dju149.","journal-title":"J Natl Cancer Inst"},{"key":"BFbcj20173_CR42","doi-asserted-by":"publisher","first-page":"932","DOI":"10.1038\/ng.924","volume":"43","author":"PP Zenatti","year":"2011","unstructured":"Zenatti PP, Ribeiro D, Li W, Zuurbier L, Silva MC, Paganin M et al. Oncogenic IL7R gain-of-function mutations in childhood T-cell acute lymphoblastic leukemia. Nat Genet 2011; 43: 932\u2013939.","journal-title":"Nat Genet"},{"key":"BFbcj20173_CR43","doi-asserted-by":"publisher","first-page":"901","DOI":"10.1084\/jem.20110580","volume":"208","author":"C Shochat","year":"2011","unstructured":"Shochat C, Tal N, Bandapalli OR, Palmi C, Ganmore I, te Kronnie G et al. Gain-of-function mutations in interleukin-7 receptor-alpha (IL7R) in childhood acute lymphoblastic leukemias. J Exp Med 2011; 208: 901\u2013908.","journal-title":"J Exp Med"},{"key":"BFbcj20173_CR44","doi-asserted-by":"publisher","first-page":"5059","DOI":"10.1038\/ncomms6059","volume":"5","author":"J Zhang","year":"2014","unstructured":"Zhang J, Cao M, Dong J, Li C, Xu W, Zhan Y et al. ABRO1 suppresses tumourigenesis and regulates the DNA damage response by stabilizing p53. Nat Commun 2014; 5: 5059.","journal-title":"Nat Commun"},{"key":"BFbcj20173_CR45","doi-asserted-by":"publisher","first-page":"106","DOI":"10.1182\/blood-2013-10-529685","volume":"124","author":"C Shochat","year":"2014","unstructured":"Shochat C, Tal N, Gryshkova V, Birger Y, Bandapalli OR, Cazzaniga G et al. Novel activating mutations lacking cysteine in type I cytokine receptors in acute lymphoblastic leukemia. Blood 2014; 124: 106\u2013110.","journal-title":"Blood"},{"key":"BFbcj20173_CR46","doi-asserted-by":"publisher","first-page":"153","DOI":"10.1111\/j.1365-2141.2008.07314.x","volume":"143","author":"P Van Vlierberghe","year":"2008","unstructured":"Van Vlierberghe P, Pieters R, Beverloo HB, Meijerink JP . Molecular-genetic insights in paediatric T-cell acute lymphoblastic leukaemia. Br J Haematol 2008; 143: 153\u2013168.","journal-title":"Br J Haematol"},{"key":"BFbcj20173_CR47","doi-asserted-by":"publisher","first-page":"758","DOI":"10.1038\/nature05690","volume":"446","author":"CG Mullighan","year":"2007","unstructured":"Mullighan CG, Goorha S, Radtke I, Miller CB, Coustan-Smith E, Dalton JD et al. Genome-wide analysis of genetic alterations in acute lymphoblastic leukaemia. Nature 2007; 446: 758\u2013764.","journal-title":"Nature"},{"key":"BFbcj20173_CR48","doi-asserted-by":"publisher","first-page":"e0164370","DOI":"10.1371\/journal.pone.0164370","volume":"11","author":"M Abaigar","year":"2016","unstructured":"Abaigar M, Robledo C, Benito R, Ramos F, Diez-Campelo M, Hermosin L et al. Chromothripsis Is a Recurrent Genomic Abnormality in High-Risk Myelodysplastic Syndromes. PLoS One 2016; 11: e0164370.","journal-title":"PLoS One"},{"key":"BFbcj20173_CR49","first-page":"4","volume":"1","author":"J Pei","year":"2012","unstructured":"Pei J, Jhanwar SC, Testa JR . Chromothripsis in a case of TP53-deficient chronic lymphocytic leukemia. Leuk Res Rep 2012; 1: 4\u20136.","journal-title":"Leuk Res Rep"},{"key":"BFbcj20173_CR50","doi-asserted-by":"publisher","first-page":"59","DOI":"10.1016\/j.cell.2011.12.013","volume":"148","author":"T Rausch","year":"2012","unstructured":"Rausch T, Jones DT, Zapatka M, Stutz AM, Zichner T, Weischenfeldt J et al. Genome sequencing of pediatric medulloblastoma links catastrophic DNA rearrangements with TP53 mutations. Cell 2012; 148: 59\u201371.","journal-title":"Cell"},{"key":"BFbcj20173_CR51","doi-asserted-by":"publisher","first-page":"1263","DOI":"10.1016\/j.bbamcr.2006.10.001","volume":"1773","author":"JA McCubrey","year":"2007","unstructured":"McCubrey JA, Steelman LS, Chappell WH, Abrams SL, Wong EW, Chang F et al. Roles of the Raf\/MEK\/ERK pathway in cell growth, malignant transformation and drug resistance. Biochim Biophys Acta 2007; 1773: 1263\u20131284.","journal-title":"Biochim Biophys Acta"},{"key":"BFbcj20173_CR52","doi-asserted-by":"publisher","first-page":"3420","DOI":"10.1182\/blood-2014-04-531871","volume":"124","author":"J Irving","year":"2014","unstructured":"Irving J, Matheson E, Minto L, Blair H, Case M, Halsey C et al. Ras pathway mutations are prevalent in relapsed childhood acute lymphoblastic leukemia and confer sensitivity to MEK inhibition. Blood 2014; 124: 3420\u20133430.","journal-title":"Blood"},{"key":"BFbcj20173_CR53","doi-asserted-by":"publisher","first-page":"3633","DOI":"10.1200\/JCO.2011.40.7783","volume":"30","author":"S Lehmann","year":"2012","unstructured":"Lehmann S, Bykov VJ, Ali D, Andren O, Cherif H, Tidefelt U et al. Targeting p53 in vivo: a first-in-human study with p53-targeting compound APR-246 in refractory hematologic malignancies and prostate cancer. J Clin Oncol 2012; 30: 3633\u20133639.","journal-title":"J Clin Oncol"},{"key":"BFbcj20173_CR54","doi-asserted-by":"publisher","first-page":"248","DOI":"10.1111\/joim.12336","volume":"277","author":"J Zawacka-Pankau","year":"2015","unstructured":"Zawacka-Pankau J, Selivanova G . Pharmacological reactivation of p53 as a strategy to treat cancer. J Intern Med 2015; 277: 248\u2013259.","journal-title":"J Intern Med"}],"container-title":["Blood Cancer Journal"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/bcj20173.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/bcj20173","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/bcj20173.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,12,22]],"date-time":"2022-12-22T17:22:24Z","timestamp":1671729744000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/bcj20173"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,2,3]]},"references-count":54,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2017,2]]}},"alternative-id":["BFbcj20173"],"URL":"https:\/\/doi.org\/10.1038\/bcj.2017.3","relation":{},"ISSN":["2044-5385"],"issn-type":[{"value":"2044-5385","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,2,3]]},"assertion":[{"value":"1 December 2016","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"12 December 2016","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"3 February 2017","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no conflict of interest.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}]}}