In a genome-sequencing study of pancreatic cancers and blood in 101 patients, at least one-third of the patients’ tumors were found to have genetic mutations that may someday help guide precision therapy of their disease. Results of blood tests to detect DNA shed from tumors were found to predict cancer recurrence more than half a year earlier than standard imaging methods.
“Pancreatic cancer has one of the highest death rates among cancer types. Many people think there are no treatment options, but our study shows that genomic sequencing of patients’ tumor samples may identify mutations that match the target of certain clinical trials or drugs that are more precisely appropriate for these patients,” said Victor Velculescu, MD, PhD, a professor of oncology and pathology at the Johns Hopkins University School of Medicine and co-director of the Kimmel Cancer Center’s Cancer Biology Program in Baltimore, Maryland.
Velculescu cautioned that, for patients to realize the treatment-guiding benefit of genomic sequencing, researchers will first need to develop larger, multi-institutional trials using experimental or approved drugs that target the mutations identified. Currently, pancreatic cancer is treated surgically and with radiation and chemotherapy.
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Results of their sequencing study, using data generated by Personal Genome Diagnostics Inc., a company co-founded by the Johns Hopkins researchers, were published in Nature Communications (2015; doi:10.1038/ncomms8686).
Pancreatic cancers are diagnosed in nearly 50,000 people in the United States each year. Fewer than 10% of them survive more than 5 years past diagnosis, and most patients are prescribed therapies based on their disease stage, not the genomic qualities of their cancer.
For the sequencing study, Velculescu and his colleagues collected tumor samples and normal DNA from 101 patients with stage 2 pancreatic cancer whose tumors were surgically removed at the University of Pennsylvania, the University of Copenhagen, and Washington University at St. Louis.
The team sequenced the whole exomes, or coding regions of the genome, of 24 of the 101 patients’ tumor and normal DNA to find genes that drive the cancer’s growth, and were commonly mutated among the group. Then, the group sequenced tumor and normal DNA in the rest of the patients, specifically looking for mutations in a subset of cancer-promoting genes.
Pancreatic cancer tissue is often difficult to sequence, and mutations are challenging to find, said co-author Mark Sausen, PhD, a former graduate student in Velculescu’s laboratory when the research was completed who is now employed by Personal Genome Diagnostics Inc. To overcome this, the team used sensitive “deep sequencing” methods that analyzed each nucleotide base more than 750 times to identify mutated genes.
In further experiments, the scientists collected blood samples every three months from 51 patients with early-stage pancreatic cancer, including 44 of the 101 subjects who were sequenced in the current study plus seven additional patients, for up to 3 years. Some 22 of the 51 (43%) had detectable levels of cancer DNA in their blood at the time of their diagnosis. Furthermore, the scientists predicted patients’ cancer recurrence after surgery 6 months earlier by looking for cancer DNA shed into the blood, compared with standard imaging.
