Sequencing results provide, for the first time, strong molecular evidence of progression from phenotypically indolent components to more aggressive disease and also show that both components can progress independently, even if they arise from the same precursor, according to the study. The paper appears online in Cancer Research.
Images of frozen lung cancer tissue (above) before laser dissection and after. The two upper-left images represent lepidic (or slow-growing) lung cancer that might be managed with less aggressive options, such as radiation or watchful waiting. The upper-right images are of invasive lung cancer, which would likely benefit from more aggressive treatments, including surgery and chemotherapy. The graph shows the number of genomic rearrangements for invasive (INV) and lepidic (L) components of lung cancer.
“This study sheds light on potential changes in our understanding of both the molecular pathogenesis and best treatment of lung adenocarcinoma,” says George Vasmatzis, Ph.D., senior author of the study and co-director of the Biomarker Discovery Program in the Mayo Clinic Center for Individualized Medicine. “The heterogeneity of lung cancer tells us repeatedly that the natural history of tumors and the roads to progression vary among cases, and multiple models are possible in certain cancers.”
Lung cancer accounts for nearly 160,000 deaths every year in the United States, more than the next three most-common cancers combined, according to the American Lung Association. Treatment of early-stage cancers may be tailored according to the type of genomic alterations observed, says Dr. Vasmatzis. In some cases, this could mean less-aggressive treatment and periods of close observation, while other situations may call for more immediate interventions, such as surgery or radiation.
“As suggested by clinical studies demonstrating improved disease-free and overall survival for treatment of lesions containing components of adenocarcinoma in situ [noninvasive lung cancer], it may be that this represents a distinct clinical entity that can be treated less aggressively by either sub-lobar resection or even periods of watchful waiting with close imaging follow-up prior to any treatment,” says Dr. Vasmatzis.
Future studies of lung cancer genomics and tumor progression are underway from Dr. Vasmatzis’ team in the Biomarker Discovery Program. Their goal is to develop a series of predictive biomarkers that can help patients and physicians separate potentially aggressive and life-threatening lung cancers from indolent ones based on the molecular signatures found within the individual patient’s tissue.
Co-authors of the paper include Stephen Murphy, Ph.D.; Dennis Wigle, M.D., Ph.D.; Joema Lima M.D.; Faye Harris; Geoffrey Halling; Michael Asiedu, Ph.D.; Charlie Seto; Simone Terra, M.D.; Farhad Kosari, Ph.D.; Tobias Peikert, M.D.; Ping Yang, M.D., Ph.D.; and Marie Christine Aubry, M.D., all of Mayo Clinic.
About Mayo Clinic
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About the Mayo Clinic Center for Individualized Medicine
The Mayo Clinic Center for Individualized Medicine is home to the Individualized Medicine Clinic, the world’s first integrated multidisciplinary genomics clinic, serving patients with advanced cancer and complex diagnoses. The center discovers and integrates the latest in genomic, molecular and clinical sciences into personalized care for each Mayo Clinic patient. Visit http://mayoresearch.mayo.edu/center-for-individualized-medicine for more information, or visit our blog at individualizedmedicineblog.mayoclinic.org/.
Sam Smith, Mayo Clinic Public Affairs, 507-284-5005,