Lymphoma- and leukemia-associated chromosomal translocations in healthy individuals

Chromosomal translocations (CTs) are hallmark mutations of hematopoietic malignancy that result in the deregulated expression of oncogenes or the generation of novel fusion genes. The polymerase chain reaction (PCR) can be used to detect illegitimate recombinations of genomic DNA sequences as a more sensitive assay than cytogenetics for determining the presence of CTs. Both direct DNA-PCR and reverse transcriptase-PCR were used to examine healthy individuals for lymphoma- and leukemia-associated CTs. Two oncogene-activating CTs [t(14;18)(q32;q21) and t(8;14)(q24;q32)] and one fusion-gene CT [t(2;5)(p23;q35)] from lymphomas and five fusion-gene CTs from leukemia [t(9;22)(q34;q11), t(4;11)(q21;q23), t(15;17)(q22;q11), t(12;21)(p13;q22), t(8;21)(q22;q22)] were detected in such studies. The biological implication is that CTs associated with malignant tumors may also be found in cells that are not neoplastic. CTs are characteristic attributes of neoplastic clones but are by themselves insufficient to cause malignant transformation. A better understanding of the special biology of non-neoplastic CT-bearing cells will provide insight into their putative role as tumor precursors. Prospective epidemiological studies are needed to determine whether such cells in healthy individuals may, in some instances, become clonogenic founders of lymphoma or leukemia.