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Chromothripsis-Mediated Structural Variations and Clonal Evolution In Recurrent Childhood High Hyperdiploid Acute Lymphoblastic Leukemia

  • High hyperdiploid acute lymphoblastic leukemia (HeH-ALL) is characterized by 51-67 chromosomes and nonrandom gains of specific chromosomes (X, 4, 6, 10, 14, 17, 18, and 21). It presents the most frequent numerical cytogenetic alteration in childhood pre B-cell ALL occurring in 25-30% of cases. Recurrent disease will affect 15-20%. Pre-leukemic HeH clones are generated in utero, but cooperating oncogenic lesions are necessary for overt leukemia and remain to be determined. Recently, a phenomenon termed chromothripsis has been described in which massive structural variations occur in a single aberrant mitosis. Whole or partial chromosomes are shattered and some fragments are lost in the process of rejoining. Thus, characteristically, chromosomal copy numbers oscillate between two copy number states. Chromothripsis has been suggested to be a tumor-driving alteration that may be present in 2-3% of all human cancers. Its role as a potential cooperating or initiating lesion in HeH-ALL has not been determined.

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Metadaten
Document Type:Article
Language:English
Author:Cai Chen, Christoph Bartenhagen, Michael Gombert, Vera Okpanyi, Vera Binder, Andrea Teigler-Schlegel, Jutta Bradtke, Silja Roettgers, Jochen Harbott, Sebastian Ginzel, Ralf Thiele, Martin Dugas, Jianda Hu, Arndt Borkhardt, Ute Fischer
Parent Title (English):Blood
Volume:122
Issue:21
First Page:233
ISSN:0006-4971
DOI:https://doi.org/10.1182/blood.v122.21.233.233
Publisher:The American Society of Hematology
Date of first publication:2013/11/15
Note:
611. Leukemias: Biology, Cytogenetics and Molecular Markers in Diagnosis and Prognosis, November 15, 2013
Departments, institutes and facilities:Fachbereich Informatik
Institut für funktionale Gen-Analytik (IFGA)
Dewey Decimal Classification (DDC):6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
Entry in this database:2015/04/02