Identifying structural variants in cancer genomes has been challenging, but now researchers from Penn State say they have developed a unique approach that will help scientists more easily find these large mutations.
Feng Yue, assistant professor of biochemistry and molecular biology, said the new method—described in a Nature Genetics paper published yesterday—could help researchers find new structural variations within cancer cell DNA and learn more about how those cancers begin.
"We were able to design and use this computational framework to connect three methods together, to get the most comprehensive view of the genome," Yue said. "Each method by itself can only review a portion of the structural variations, but when you integrate the results of the three different methods, you can get the most comprehensive view of the cancer genome."
The researchers used three existing methods for finding structural variants: optical mapping, high-throughput chromosome conformation capture (Hi-C), and whole genome sequencing, which has been used to discover the majority of structural variants that are already known. Using their new method, the researchers were able to find structural variations for over 30 types of cancer cells. The team of scientists was also able to use the same methods to begin to learn why certain classes of structural variants may be contributing to cancers.
"Many of the structural variants that are found in human cancers do not appear to directly impact a gene," said Jesse Dixon, a fellow at the Salk Institute in San Diego, and one of the co-authors of the work. "Instead, many structural variants appear in non-coding portions of the genome, what people have historically referred to as junk DNA, and it can be a bit of a mystery as to why these may be contributing to cancer."
What the researchers were able to observe is that some structural variants appear to affect regulatory gene "switches" in noncoding sequences of DNA. Defective switches prevent appropriate turning on or off of specific genes and this can contribute to cancer. "With many cancers, the gene itself is OK but the 'switch' that controls it is what's causing problems," Yue said. "Using our approach, it's possible that we could find out that the switch was broken and find a cure based on the specific target for that switch. If it's switched off, for example, maybe we could use gene editing technology to turn it back on."