A DNA damage repair mechanism is involved in the origin of chromosomal translocations t(4;11) in primary leukemic cells

• Published in: Oncogene Vol. 18; no. 33; pp. 4663 - 4671
• Main Authors: GILLERT, E, LEIS, T, GRIESINGER, F, GREIL, J, FEY, G. H, MARSCHALEK, R, REPP, R, REICHEL, M, HÖSCH, A, BREITENLOHNER, I, ANGERMÜLLER, S, BORKHARDT, A, HARBOTT, J, LAMPERT, F
• Format: Journal Article
• Language: English
• Published: Basingstoke Nature Publishing 19.08.1999; Nature Publishing Group
• Subjects: Adolescent; Adult; Base Sequence; Biological and medical sciences; Biopsy; Breakpoints; Burkitt Lymphoma - etiology; Burkitt Lymphoma - genetics; Cell physiology; Cell transformation and carcinogenesis. Action of oncogenes and antioncogenes; Child; Child, Preschool; Children; Chromosome translocations; Chromosomes; Chromosomes, Human, Pair 11; Chromosomes, Human, Pair 4; Deoxyribonucleic acid; DNA; DNA Damage; DNA Repair; DNA-Binding Proteins - genetics; Female; Fundamental and applied biological sciences. Psychology; Hematologic and hematopoietic diseases; Histone-Lysine N-Methyltransferase; Humans; Immune system; Infant; Leukemia; Leukemia, B-Cell - etiology; Leukemia, B-Cell - genetics; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis; Lymphocytes T; Lymphoma; Male; Medical sciences; Molecular and cellular biology; Molecular Sequence Data; Myeloid-Lymphoid Leukemia Protein; Nuclear Proteins - genetics; Nucleotides; Precursor B-Cell Lymphoblastic Leukemia-Lymphoma - etiology; Precursor B-Cell Lymphoblastic Leukemia-Lymphoma - genetics; Proto-Oncogenes; T cell receptors; Transcription Factors; Transcriptional Elongation Factors; Translocation, Genetic; Chromosomal aberration; Human; Acute; Malignant hemopathy; Carcinogenesis; Case study; Lymphoproliferative syndrome; DNA; Abnormal chromosome; Acute lymphocytic leukemia; Lesion; Repair; Chromosome translocation
• ISSN: 0950-9232; 1476-5594
• DOI: 10.1038/sj.onc.1202842

Some chromosomal translocations involved in the origin of leukemias and lymphomas are due to malfunctions of the recombinatorial machinery of immunoglobulin and T-cell receptor-genes. This mechanism has also been proposed for translocations t(4;11)(q21;q23), which are regularly associated with acute pro-B cell leukemias in early childhood. Here, reciprocal chromosomal breakpoints in primary biopsy material of fourteen t(4;11)-leukemia patients were analysed. In all cases, duplications, deletions and inversions of less than a few hundred nucleotides indicative of malfunctioning DNA repair mechanisms were observed. We concluded that these translocation events were initiated by several DNA strand breaks on both participating chromosomes and subsequent DNA repair by 'error-prone-repair' mechanisms, but not by the action of recombinases of the immune system.