Scientists at Johns Hopkins University have identified what they believe are among the earliest "premalignant" genetic changes marking the potential onset of the most common and fatal form of lung cancer, adenocarcinoma.
Examining very tiny premalignant lesions of the lung, the research team discovered DNA alterations that can be detected long before any diagnosis of invasive clinical cancer would be made. A report on the findings was published Sept. 16 in the journal Nature Communications.
"We have a glimpse into the future in which we can detect premalignant lesions of the lung before they become tumors," says study lead author Evgeny Izumchenko, a postdoctoral fellow at the Johns Hopkins School of Medicine. But he adds that this is "only the beginning of a long road we must travel to figure out how to interpret these discoveries to use them optimally in the clinic."
Adenocarcinoma is usually diagnosed after it has spread. The average five-year survival rate is 15 percent, even with the most advanced treatment.
The prevailing opinion among lung cancer experts is that adenocarcinoma develops from microscopic lesions that accumulate multiple genetic alterations over time. The problem for scientists, especially for treatment, is the inconsistency: some of these precancerous lesions regress and disappear over time, while others progress to cancer.
To help predict which of the lesions develop into cancer, the scientists collected multiple tissue samples from six patients undergoing surgical removal of lung tumors.
Then [William Westra]http://www.hopkinsmedicine.org/profiles/results/directory/profile/0005286/william-westra), a professor of pathology at JHU, went through the tissue samples to single out tiny precancerous lung lesions known as atypical adenomatous hyperplasia. The DNA derived from these microscopic lesions and other lesions in different phases of progression were sequenced to pinpoint genetic abnormalities, which occurred long before the lesions would become recognized as adenocarcinoma of the lung.
Using a technique known as targeted next-generation sequencing, the researchers found that in three patients, the same DNA mutations were shared between premalignant lesions and cancerous tumors within the same lung. Finding this definitive link suggests that those specific mutations might cause tumors to progress. Researchers plan further studies to confirm the findings in a greater number of lung cancer patients.
"This study takes detection to a whole new level in terms of size of the lesion," says David Sidransky, a professor of otolaryngology, oncology, and pathology who directs the head and neck cancer research at Johns Hopkins.
Researchers also examined patients' blood and sputum—a mix of saliva and mucus coughed up from the respiratory tract—using ultra-sensitive digital polymerase chain reactions. In doing so, they found proof that genetic mutations associated with precancerous lesions can be detected in paired bodily fluid DNA—even before they invade and become malignant.
"We believe we were able to detect, for the first time, DNA circulating in the blood from precancerous lesions of the lung," says Mariana Brait, an assistant professor of otolaryngology-head and neck surgery at Johns Hopkins.
This detection capacity could suggest it as a potential companion test to a biopsy, offering more knowledge for treatment.
When the team further explored different regions within the same lesion, they found other genetic mutations that are known to have different responses and outcomes from various types of cancer treatment. The discovery highlights the limitations of the single biopsies typically used to dictate patients' therapies, Sidransky says.Read more from Hopkins Medicine
Posted in Health, Science+Technology
Tagged cancer, lung cancer