Scientists Pioneer Technology to Detect More Chromosomal Aberrations in Cancer Tumors

Jinghui Zhang, PhD

Researchers at St. Jude Children’s Research Hospital and Washington University Pediatric Cancer Genome Project have discovered a way to detect more chromosomal aberrations in tumors.

The investigators developed a computer tool that is dramatically better for finding genetic missteps that promote cancer. Researchers found that by using a new algorithm, they were able to identify chromosomal rearrangements and DNA insertions or deletions unique to cancer.

This cutting edge computational approach is called CREST (Clipping Reveals Structure). Using the CREST technology, researchers found 89 new structural differences in cancer genomes of 5 patients with a subtype of acute lymphoblastic leukemia (ALL), called T-lineage ALL. The investigators also examined genetic samples from melanoma patients and were able to identify 50 new variations in melanoma cells.

The results of the study were published online in the June 12th issue of Nature Methods.

Shortly after the study began in 2010, Jinghui Zhang, PhD, an associate member of the St. Jude Department of Computational Biology and the study’s senior author noticed that there needed to be new means of identifying genomic variations that lead to cancer. “CREST is significantly more accurate and sensitive than existing methods of finding structural variations in next-generation sequencing data. It finds differences between a patient’s normal and cancer genomes other tools cannot find,” Zhang said.

Li Ding, PhD,

Zhang and her colleagues began work on CREST after they manually detected a chromosomal rearrangement involving a known cancer gene that existing analytic tools did not detect. “Similar tools miss up to 60 to 70% of these structural rearrangements in tumors. CREST ensures that scientists will be able to find important structural variations that play critical roles in tumor formation.”

This next-generation sequencing technology breaks double-stranded DNA into millions of smaller fragments, which are then copied about 30 times. Those segments are then reassembled, using the human genome as a reference. Researchers were interested in where a patient’s normal and cancer genomes differ because they believe those differences include the cancer’s origin.

“With the incorporation of CREST, we now can augment the existing approaches we have developed at Washington University to better detect and analyze important structural variants in human cancers,” said coauthor Li Ding, PhD, the assistant director of medical genomics at Washington University’s Genome Institute.

Wang J, Mullighan CG, Easton J, et al. CREST maps somatic structural variation in cancer genomes with base-pair resolution. [Published online ahead of print June 12, 2011]. Nat Methods. 2011. doi:10.1038/nmeth.1628.