Biomarkers Created from Tumor DNA

The study's findings reveal that next-generation sequencing technology is poised become an important tool in the new era of personalized management of cancer patients.

"There is currently no test for cancer patients that provide personalized biomarkers for clinical management of disease, and we feel that this is an important step in bringing new genome sequencing technologies to personalized patient care,” said senior author Victor Velculescu, associate professor of oncology and codirector of the Cancer Biology Program at Johns Hopkins University (Baltimore, MD, USA).

Keeping cancer cells under control requires the ability to monitor residual and recurrent tumors to evaluate whether or not treatment is working. Based on discovering cancer-related changes in DNA, the personalized analysis of rearranged ends (PARE) approach provides a very accurate and specific way to monitor tumors, by searching for the genetic breadcrumb trail left by lingering cancer cells after surgery or during drug therapy. "We believe that this is one of the first applications of new genome sequencing technologies that could be useful for cancer patients,” stated Dr. Velculescu.

A nearly universal characteristic of human cancer is the widespread rearrangement of DNA. Yet, historically it has been difficult to map effectively such changes in individual tumors. Now, Dr. Velculescu and a team of colleagues from Johns Hopkins University and Life Technologies Corp. (Carlsbad, CA, USA) have utilized PARE to identify a handful of rearranged DNA sequences in four colorectal and two breast tumors.

Since these rearranged sequences are not present in normal DNA (only in tumor DNA), the researchers were able to create personalized biomarkers or "red flags” based on these unique sequences. They used the biomarkers to search for tiny amounts of tumor DNA meshed within large quantities of normal DNA in blood and other bodily fluid samples--as could easily be done following surgical removal of tumors or other therapies.

"PARE uses genetic characteristics unique to the tumor to monitor disease progression. By exploiting rearrangements specific to the patient's tumor, we have developed a personalized approach for detection of residual disease,” said coauthor Rebecca Leary, graduate student at the Johns Hopkins Kimmel Cancer Center.

PARE is expensive, however--a tough barrier to cross in the shift towards wide clinical application. Nonetheless, this approach may profoundly alter how the effectiveness of cancer treatments such as radiation, chemotherapy, and surgery are evaluated in individual patients. "As PARE becomes affordable, it will be a helpful addition for physicians to tailor patient care and may become a useful supplement to traditional monitoring by imaging or other approaches,” concluded Dr. Leary.

The study was published in the 24 February 24, 2010, issue of the journal Science Translational Medicine.

Related Links:
Johns Hopkins University
Life Technologies