Wednesday, July 6, 2011

Quantification of t(14;18) in the lymphocytes of healthy adult humans as a possible biomarker for environmental exposures to carcinogens.



A t(14;18) chromosomal translocation is found in approximately 85% of follicular lymphomas by both cytogenetic and molecular analyses. This rearrangement deregulates expression of the bcl-2 proto-oncogene by translocation into the immuno-globulin heavy chain locus and is probably mediated by illegitimate V(D)J recombination. We have developed a quantitative nested PCR method for detecting this event in lymphocytes of healthy individuals. Genomic DNA is purified from peripheral blood lymphocytes, and 2.5 microg (representing 4 X 10(5) cells) are amplified with translocation-specific primers under conditions in which a single copy, if present, will give a detectable PCR product. Multiple replicates are analyzed for each individual, and Poisson statistics are then used to estimate the translocation mutant frequency. We have examined lymphocyte DNA from 34 healthy individuals by this assay and found the frequency of cells with t(14;18) to range from <0.8-96X10(-7). The molecular nature of the translocations has been investigated by determining the DNA sequence at the translocation junctions. In several individuals, multiple isolates of the same translocation event were recovered, indicating that the cell with the original translocation had undergone clonal expansion. In addition, multiple independent translocations were shown to occur within an individual. Since this translocation appears to be one step in the progression of a normal cell to a cancer cell, this assay may have utility as an effects biomarker for environmental carcinogen exposure.

[comments by connie:  So, here is a test that can detect possible cancers from blood lymphocytes-T (14;18) which was discussed by the committee on mutagencity/genotoxicty.  This will go on my to do list to discuss with my surgeon.  The question is, if there is concern regarding the possible association of metal induced cancers with total hip replacement (THA) that suggest that there is an increased risk of lymphoma and leukemia in patients with THA (reference was the jenkins article I published a few days ago) , how do you test for that?   While none of us likely understand the terminology in the above abstract, this is a test that I would like to have a  look at.  I  have been looking for some more recent methodologies but have found none....yet.
The other thing I find interesting about this is, my prior understanding was that "environmental" cancer data/testing is not readily portable to understanding hip stuff.  Well, I think we need to question that.  If there is a way to measure these chromosome translocations that are purportedly associated with metal induced cancers, then why would we not want to test this?
(In genetics, a chromosome translocation is a chromosome abnormality caused by rearrangement of parts between nonhomologous chromosomes. A gene fusion may be created when the translocation joins two otherwise separated genes, the occurrence of which is common in cancer.)]

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