This improved chromosomal analysis may help physicians better assess a patient's prognosis and likelihood to respond to a given treatment.
Plasma cell proliferative disorders, or PCPD, account for approximately 10 percent of all blood born cancers that range from the very slow-growing smoldering myeloma to a very aggressive plasma cell leukemia.
The study will be presented by Ryan Knudson of the Mayo Clinic Cytogenetics Laboratory at 6:30 p.m., CDT, Wednesday, Oct. 24.
FISH, which stands for fluorescence in situ hybridization, detected chromosomal abnormalities in 67 percent of 1,548 patients with suspected PCPD. Conventional chromosomal analysis detected abnormalities in only 10 percent of the same patients. The FISH test is designed to detect genetic abnormalities in plasma cells whereas other conventional methods typically looks within any cell type that is present, says the lead author of the study, Rhett Ketterling, M.D., a Mayo Clinic pathologist and geneticist who specializes in chromosomes and chromosomal abnormalities.
This test is a marked improvement over conventional chromosomal analysis and has become readily accepted into the diagnostic algorithm in patients with PCPD at Mayo Clinic and at other leading academic institutions, Dr. Ketterling says.
The test should be applied to patients diagnosed with PCPD, particularly multiple myeloma, to determine the presence of genetic abnormalities that could offer insight into prognosis, he states.
Our results show that a targeted plasma-cell specific FISH analysis is an important method for detecting common genetic abnormalities typically seen in patients with multiple myeloma, Dr. Ketterling says.
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The conference showed how fundamental breakthroughs can be exploited in tackling disease. One of the most exciting discoveries of recent years is the fact that rods and cones are not the only light receptors in the eye, overturning the long established view. There is also a receptor, called phototropin, that recognises blue light at much lower levels, even operating in some people who are otherwise blind, playing an important role in setting the circadian clock. At the conference, one of the world's leading specialists in chronobiology (study of biologicalrhythms) Russell Foster, explained how mouse models were being used to study this newly discovered blue light receptor. "This has been analysed in mice and he is using the knowledge gained to interact with ophthalmologists (eye disease specialists) and patients," said Sang.
Genes determine individual traits not just through their variations, or alleles, but also through differing levels of expression. Another important field of research discussed at the conference concerned the important role of microRNAs in controlling gene expression. RNAs are normally the intermediate molecules between DNA and their products, proteins, in gene expression. However microRNA is a type of RNA that instead of being involved in protein production, feeds back into the DNA coding process to regulate the expression of other genes. Mutations in the genes coding for the microRNA itself can therefore effect the expression of other genes, with some subtle and occasionally dramatic effects, as Sang pointed out. Given that animals inherit two copies, or alleles, of each gene, mutations are more likely to be effective when one of the copies is already silenced, as happens in the phenomenon known as genomic imprinting. Sang cited the case of sheep, where imprinting of a gene called callipyge leads to increased muscle growth in the hindquarters, which clearly can be a desirable trait in meat production.
All these different strands of research could benefit from being integrated into a common framework to avoid duplication of effort and exploit relevant expertise, according to Sang. "The main value of the workshop was that it brought the more theoretical people together with experimental scientists and opportunities for synergies were identified."
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