Molecular subtypes and genetic alterations may determine response to lung cancer therapy

A UNC-led team of scientists has shown for the first time that lung cancer molecular subtypes correlate with distinct genetic alterations and with patient response to therapy. These findings in pre-clinical models and patient tumor samples build on their previous report of three molecular subtypes of non-small cell lung cancer and refines their molecular analysis of tumors.

Their findings were published in the May 10, 2012 online edition of the Public Library of Science One.

Study senior author, Neil Hayes, MD, MPH, associate professor of medicine, says, "It has been known for about a decade of using gene expression arrays that "molecular subtypes" exist. These subtypes have molecular "fingerprints" and frequently have different clinical outcomes. However, the underlying etiologies of the subtypes have not been recognized. Why do tumors form subtypes?

"Our study shows that tumor subtypes have different underlying alterations of DNA as part of the difference. These differences are further evidence of the importance of subtypes and the way we will use them. For example, the mutations are different which may imply much more ability to target than previously recognized. Also, we are starting to get a suggestion that these subtypes may reflect different cells of origin that rely on different cancer pathways. This is further unlocking the diversity of this complex disease." Hayes is a member of UNC Lineberger Comprehensive Cancer Center.

The team first defined and reported in 2006 on three lung cancer molecular subtypes, named according to their genetic pattern -- bronchoid, squamoid and magnoid.

In this PLoS One paper they sought to determine if distinct genetic mutations co-occur with each specific molecular subtypes. They found that specific genetic mutations were associated with each subtype and that these mutations may have independent predictive value for therapeutic response.

Additional UNC authors are: Matthew Wilkerson, PhD; Xiaoying Yin, MD; Vonn Walter, PhD: Ni Zhao, MS; Christopher Cabanski, PhD; Michele Hayward, RD; Ryan Miller, MD, PhD; Alden Parsons, MD; Leigh Thorne, MD; Benjamin Haithcock, MD; Nirmal Veeramachaneni, MD; William Funkhouser, MD; Scott Randell, PhD; and Charles Perou, PhD. Additional authors are from the University of Utah Health Sciences Center and Pittsburgh Cancer Institute.

Funding for the study was provided by the National Cancer Institute and the National Heart, Lung and Blood Institute, member institutes of the National Institutes of Health; Joan's Legacy Foundation; and a UNC Lineberger Clinical/Translational Developmental Research Award.