Sequencing cell-free tumor DNA from a patient’s blood can identify chromosomal alterations that can aid in the diagnosis of cancer, as well as the selection of treatment and monitoring for cancer recurrence. This proof-of-principle may ultimately lead to a universal blood-based screening test for cancer and the ability to treat cancer without invasive biopsies, according to the authors of a study published in Science Translational Medicine. The authors used massively parallel whole-genome sequencing to compare circulating cell-free DNA from 10 late-stage colorectal cancer and breast cancer patients to 10 healthy subjects. The researchers were able to detect chromosomal aberrations (both copy number changes and rearrangements) in plasma from all of the patients. The detected alterations included amplification of cancer-driving genes ERBB2 and CDK6, both targetable with anti-cancer drug treatments. The copy number variations observed from DNA in blood samples matched samples from resected tumor in three of the colorectal cases, whose tumors were analyzed. “Rearrangements and copy number changes are the hallmarks of cancer and we were able to find both in every case without knowing if the patient had cancer,” says Victor Velculescu, M.D., Ph.D., co-director of the Cancer Biology Program at Johns Hopkins University (Baltimore) and co-author of […]
Sequencing cell-free tumor DNA from a patient’s blood can identify chromosomal alterations that can aid in the diagnosis of cancer, as well as the selection of treatment and monitoring for cancer recurrence. This proof-of-principle may ultimately lead to a universal blood-based screening test for cancer and the ability to treat cancer without invasive biopsies, according to the authors of a study published in Science Translational Medicine.
The authors used massively parallel whole-genome sequencing to compare circulating cell-free DNA from 10 late-stage colorectal cancer and breast cancer patients to 10 healthy subjects. The researchers were able to detect chromosomal aberrations (both copy number changes and rearrangements) in plasma from all of the patients. The detected alterations included amplification of cancer-driving genes ERBB2 and CDK6, both targetable with anti-cancer drug treatments. The copy number variations observed from DNA in blood samples matched samples from resected tumor in three of the colorectal cases, whose tumors were analyzed.
“Rearrangements and copy number changes are the hallmarks of cancer and we were able to find both in every case without knowing if the patient had cancer,” says Victor Velculescu, M.D., Ph.D., co-director of the Cancer Biology Program at Johns Hopkins University (Baltimore) and co-author of the study. “We have developed a way to identify cancer from circulating tumor DNA without scans, without invasive biopsies.”
Additionally, the authors quantified their ability to discriminate between cancer patients and healthy subjects by analyzing simulated mixtures of varying concentrations of tumor and control DNA. Tumor DNA could be detected at concentrations as low as 0.75 percent in the plasma of patients (sensitivity >90 percent and a specificity >99 percent). The authors acknowledge though, that in early-stage cancers, circulating concentrations may be lower and more difficult to detect without more extensive sequencing, as the sensitivity and specificity parameters were dependent on the amount of sequence data obtained.
Velculescu tells DTTR that perhaps in five years it would be possible to give 40-year-olds a blood-based screening test to identify if they have an early form of cancer. Such a test is still too expensive with current sequencing approaches, but the technology could begin to be implemented into clinical care for management of medium to late-stage cancers “in the next couple years.”
