Using a technique developed by Horvitz and his colleagues, they then amplified the miRNA from target cells, applied it to the beads and stained it. Using a cell-sorting technique, they determined the identity of each miRNA by its bead color and the abundance of each by the intensity of the stain on each bead.
Using the new techniques, the researchers discovered that they could distinguish a diverse range of human cancer cells from one another on the basis of their miRNA expression patterns alone. They could also use miRNA activity patterns to distinguish subtypes of acute lymphoblastic leukemia, which differ in their genetic origin.
"These findings were both surprising and interesting, because with standard microarray analysis of messenger RNA, for every different question that you want to ask, you use totally different mRNAs that are informative for that particular question. So, it would be simply out of the question to find two hundred messenger RNAs that would be universal indicators of characteristics of cancers," Golub said.
The researchers also tested their technique on cancers that present particular diagnostic challenges, because they appear very similar under the microscope. In those studies, they found that they could classify such cancers with good accuracy. They also found that the technique could distinguish tumors from normal cells, with most miRNAs suppressed in tumors.
Finally, working with Jacks, the researchers tested how effective the technique was in distinguishing tumors from normal cells taken from mutant mice with lung cancer. "Our concern was that our previous findings might have been artifacts, because some of the tumors came from one source and the normal cells from another," said Golub. However, he said, the animal studie
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Contact: Jim Keeley
keeleyj@hhmi.org
301-215-8858
Howard Hughes Medical Institute
8-Jun-2005