Molecular structure of double reciprocal translocations: significance in B-cell lymphomagenesis.
The molecular structure of reciprocal translocations associated with low grade and high grade non-Hodgkin's lymphomas occurring together was analysed in two tumors. Sequential biopsies documented histological transformation of a large cell lymphoma to an immunoblastic lymphoma bearing t(14;18)(q32;q21) and t(8;22)(q24;q11). A second tumor, a small non-cleaved cell lymphoma, demonstrated a t(8;14)(q24;q11) as well as t(18;22)(q21;q11). DNA analysis from these tumors showed rearrangements at the Ig heavy chain, kappa and lambda light chains, BCL2 and c-MYC loci. Utilizing multiple enzyme digests and different probes spanning the BCL2, c-MYC and Ig genes, mapping of DNA break-points was performed. In both these tumors primary translocation events dysregulating the BCL2 or c-MYC were identified to have occurred in a pre-B-cell. Based on these results and those published previously, a sequence of B-cell development during which somatic recombination errors lead to the genesis of specific translocations is proposed. From these studies it is inferred that secondary dysregulation of a c-MYC in a lymphoma tumor carrying dysregulated BCL2 gene leads to rapid progression to high grade disease.
Koduru
P R
PR
Laboratory of Cancer Genetics and Cytogenetics, Memorial Sloan-Kettering Cancer Center, New York, New York.
Offit
K
K
D001706:Biopsy; D015139:Blotting, Southern; D002454:Cell Differentiation; D002471:Cell Transformation, Neoplastic / Q000235:genetics; D002883:Chromosomes, Human, Pair 14; D002887:Chromosomes, Human, Pair 18; D002892:Chromosomes, Human, Pair 22; D002898:Chromosomes, Human, Pair 8; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D016393:Lymphoma, B-Cell / Q000235:genetics*; D015183:Restriction Mapping; D013234:Stem Cells / Q000502:physiology; D014178:Translocation, Genetic