Next-generation-sequencing of recurrent childhood high hyperdiploid acute lymphoblastic leukemia reveals mutations typically associated with high risk patients

Chen C, Bartenhagen C, Gombert M, Okpanyi V, Binder V, Röttgers S, Bradtke J, Teigler-Schlegel A, Harbott J, Ginzel S, Thiele R, et al. (2015)
Leukemia research.

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: 20% of children suffering from high hyperdiploid acute lymphoblastic leukemia develop recurrent disease. The molecular mechanisms are largely unknown. Here, we analyzed the genetic landscape of five patients at relapse, who developed recurrent disease without prior high-risk indication using whole-exome- and whole-genome-sequencing. Oncogenic mutations of RAS pathway genes (NRAS, KRAS, FLT3, n=4) and deactivating mutations of major epigenetic regulators (CREBBP, EP300, each n=2 and ARID4B, EZH2, MACROD2, MLL2, each n=1) were prominent in these cases and virtually absent in non-recurrent cases (n=6) or other pediatric acute lymphoblastic leukemia cases (n=18). In relapse nucleotide variations were detected in cell fate determining transcription factors (GLIS1, AKNA). Structural genomic alterations affected genes regulating B-cell development (IKZF1, PBX1, RUNX1). Eleven novel translocations involved the genes ART4, C12orf60, MACROD2, TBL1XR1, LRRN4, KIAA1467, and ELMO1/MIR1200. Typically, patients harbored only single structural variations, except for one patient who displayed massive rearrangements in the context of a germline tumor suppressor TP53 mutation and a Li-Fraumeni syndrome-like family history. Another patient harbored a germline mutation in the DNA repair factor ATM. In summary, the relapse patients of our cohort were characterized by somatic mutations affecting the RAS pathway, epigenetic and developmental programs and germline mutations in DNA repair pathways.
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Leukemia research
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Chen C, Bartenhagen C, Gombert M, et al. Next-generation-sequencing of recurrent childhood high hyperdiploid acute lymphoblastic leukemia reveals mutations typically associated with high risk patients. Leukemia research. 2015.
Chen, C., Bartenhagen, C., Gombert, M., Okpanyi, V., Binder, V., Röttgers, S., Bradtke, J., et al. (2015). Next-generation-sequencing of recurrent childhood high hyperdiploid acute lymphoblastic leukemia reveals mutations typically associated with high risk patients. Leukemia research. doi:10.1016/j.leukres.2015.06.005
Chen, C., Bartenhagen, C., Gombert, M., Okpanyi, V., Binder, V., Röttgers, S., Bradtke, J., Teigler-Schlegel, A., Harbott, J., Ginzel, S., et al. (2015). Next-generation-sequencing of recurrent childhood high hyperdiploid acute lymphoblastic leukemia reveals mutations typically associated with high risk patients. Leukemia research.
Chen, C., et al., 2015. Next-generation-sequencing of recurrent childhood high hyperdiploid acute lymphoblastic leukemia reveals mutations typically associated with high risk patients. Leukemia research.
C. Chen, et al., “Next-generation-sequencing of recurrent childhood high hyperdiploid acute lymphoblastic leukemia reveals mutations typically associated with high risk patients”, Leukemia research, 2015.
Chen, C., Bartenhagen, C., Gombert, M., Okpanyi, V., Binder, V., Röttgers, S., Bradtke, J., Teigler-Schlegel, A., Harbott, J., Ginzel, S., Thiele, R., Husemann, P., Krell, P., Borkhardt, A., Dugas, M., Hu, J., Fischer, U.: Next-generation-sequencing of recurrent childhood high hyperdiploid acute lymphoblastic leukemia reveals mutations typically associated with high risk patients. Leukemia research. (2015).
Chen, Cai, Bartenhagen, Christoph, Gombert, Michael, Okpanyi, Vera, Binder, Vera, Röttgers, Silja, Bradtke, Jutta, Teigler-Schlegel, Andrea, Harbott, Jochen, Ginzel, Sebastian, Thiele, Ralf, Husemann, Peter, Krell, Pina, Borkhardt, Arndt, Dugas, Martin, Hu, Jianda, and Fischer, Ute. “Next-generation-sequencing of recurrent childhood high hyperdiploid acute lymphoblastic leukemia reveals mutations typically associated with high risk patients”. Leukemia research (2015).

7 Zitationen in Europe PMC

Daten bereitgestellt von Europe PubMed Central.

RAS pathway mutations as a predictive biomarker for treatment adaptation in pediatric B-cell precursor acute lymphoblastic leukemia.
Jerchel IS, Hoogkamer AQ, Ariës IM, Steeghs EMP, Boer JM, Besselink NJM, Boeree A, van de Ven C, de Groot-Kruseman HA, de Haas V, Horstmann MA, Escherich G, Zwaan CM, Cuppen E, Koudijs MJ, Pieters R, den Boer ML., Leukemia 32(4), 2018
PMID: 28972594
Outcome of relapse after allogeneic HSCT in children with ALL enrolled in the ALL-SCT 2003/2007 trial.
Kuhlen M, Willasch AM, Dalle JH, Wachowiak J, Yaniv I, Ifversen M, Sedlacek P, Guengoer T, Lang P, Bader P, Sufliarska S, Balduzzi A, Strahm B, von Luettichau I, Hoell JI, Borkhardt A, Klingebiel T, Schrappe M, von Stackelberg A, Glogova E, Poetschger U, Meisel R, Peters C., Br J Haematol 180(1), 2018
PMID: 29193007
The association of AKNA gene polymorphisms with knee osteoarthritis suggests the relevance of this immune response regulator in the disease genetic susceptibility.
Martínez-Nava GA, Fernández-Torres J, Martínez-Flores K, Zamudio-Cuevas Y, Clavijo-Cornejo D, Espinosa-Morales R, Lozada CA, Gutierrez M, Granados J, Pineda C, Madrid-Marina V, López-Reyes A., Mol Biol Rep 45(2), 2018
PMID: 29368274
ZNF384-related fusion genes define a subgroup of childhood B-cell precursor acute lymphoblastic leukemia with a characteristic immunotype.
Hirabayashi S, Ohki K, Nakabayashi K, Ichikawa H, Momozawa Y, Okamura K, Yaguchi A, Terada K, Saito Y, Yoshimi A, Ogata-Kawata H, Sakamoto H, Kato M, Fujimura J, Hino M, Kinoshita A, Kakuda H, Kurosawa H, Kato K, Kajiwara R, Moriwaki K, Morimoto T, Nakamura K, Noguchi Y, Osumi T, Sakashita K, Takita J, Yuza Y, Matsuda K, Yoshida T, Matsumoto K, Hata K, Kubo M, Matsubara Y, Fukushima T, Koh K, Manabe A, Ohara A, Kiyokawa N, Tokyo Children’s Cancer Study Group (TCCSG)., Haematologica 102(1), 2017
PMID: 27634205
The Role of Histone Protein Modifications and Mutations in Histone Modifiers in Pediatric B-Cell Progenitor Acute Lymphoblastic Leukemia.
Janczar S, Janczar K, Pastorczak A, Harb H, Paige AJ, Zalewska-Szewczyk B, Danilewicz M, Mlynarski W., Cancers (Basel) 9(1), 2017
PMID: 28054944
CD36-positive B-lymphoblasts Predict Poor Outcome in Children With B-lymphoblastic Leukemia.
Newton JG, Horan JT, Newman S, Rossi MR, Ketterling RP, Park SI., Pediatr Dev Pathol 20(3), 2017
PMID: 28521628
HIF1A (rs11549465) and AKNA (rs10817595) Gene Polymorphisms Are Associated with Primary Sjögren's Syndrome.
Hernández-Molina G, Rodríguez-Pérez JM, Fernández-Torres J, Lima G, Pérez-Hernández N, López-Reyes A, Martínez-Nava GA., Biomed Res Int 2017(), 2017
PMID: 28484714

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