Presence of cell lineage-specific hypomethylated sites in the major breakpoint cluster region.
To examine the role of DNA methylation in breakpoint location of chromosomal translocation, HpaII sites in and flanking the M-bcr on chromosome 22 were mapped in DNA from blood granulocytes and lymphocytes, bone marrow cells, thymic tissue, and spermatozoa from normal individuals. Allelic HpaII sites were identified clustered in a 600-base pair genomic area of the M-bcr. Bone marrow cells and blood granulocyte DNA showed identical allelic patterns. Thymic tissue and blood lymphocytes showed identical allelic patterns distinct from bone marrow cells and blood granulocytes. Spermatozoa showed a third methylation pattern. In all individuals, the HpaII sites were present within the BamHI/BglII fragment of the M-bcr, the same area associated with high breakpoint frequency in chronic myelogenous leukemia (CML). Three of 15 patients with chronic phase CML showed fully methylated rearranged BglII/BglII M-bcr restriction fragments not seen in normal bone marrow cells. These methylation patterns of the M-bcr may be important in CML breakpoint location and may be a marker for tissue differentiation.
Litz
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CE
Department of Laboratory Medicine and Pathology, University of Minnesota Medical School, Minneapolis 55455.
Goldfarb
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AN
Strickler
J G
JG
Brunning
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RD
D015139:Blotting, Southern; D004247:DNA / Q000097:blood / Q000235:genetics* / Q000302:isolation & purification; D006098:Granulocytes / Q000032:analysis; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000097:blood / Q000235:genetics; D007962:Leukocytes / Q000032:analysis*; D008214:Lymphocytes / Q000032:analysis; D008745:Methylation; D009693:Nucleic Acid Hybridization; D012016:Reference Values; D015183:Restriction Mapping
D004247:DNA