DNA palindromes appear frequently and are widespread in human cancers, and identifying them could help advance the understanding of genomic instability, according to researchers writing in an advanced online publication of
While the scientists did not find similar widespread palindrome formation in four normal cell lines studied, "I anticipate we will identify palindromes on the somatic chromosomes of normal cells that might not have been mapped yet," coauthor Stephen Tapscott of the Fred Hutchinson Cancer Research Center in Seattle told
In 2002, Meng-Chao Yao, also of the Hutchinson Center, and colleagues found the molecular mechanisms for palindrome formation in the protozoan
In the current
"The sensitivity is terrific, able to detect signal in a 1:40 dilution from a cell line containing only a couple of copies of the palindrome," Maria Jasin of Memorial Sloan-Kettering Cancer Center in New York, who did not participate in this study, told
In the Colo320DM human colon cancer cell line, Tapscott and colleagues found 150 genes tested significantly higher for palindromes than baseline, with significant overlap of palindrome-positive genes with breast cancer cell line MCF7. While most of the palindrome-positive genes seen in Colo320DM and MCF7 are not linked with an increase in gene copy number, as a whole these genes are more likely than any other loci to be amplified.
This indicates "only certain regions might be susceptible to further gene amplification. So the location of a tumor's palindromes might determine its ability to amplify genes and progress to higher stages of cancer," Tapscott said.
Tapscott anticipated that others might criticize the findings because the technique might be measuring unknown features aside from palindromes. "But those features, if they exist, are structures not yet imagined yet," Yao said. The researchers plan experiments with more saturating, as-yet-to-be-determined array technologies to identify where the posited palindrome centers are to directly verify their structures. In the near term, they also hope to determine the biological significance of the palindromes in tumor progression or potential.
"Their array looks at underlying genomic structure and on a genome-wide scale and high-throughput fashion, and that is really quite new," Thoas Fioretos of Lund University Hospital in Sweden, who did not participate in the study, told