A UNC-led team of scientists has shown for the first time that lungcancer molecular subtypes correlate with distinct geneticalterations and with patient response to therapy. These findings inpre-clinical models and patient tumor samples build on theirprevious report of three molecular subtypes of non-small cell lungcancer and refines their molecular analysis of tumors. Their findings were published in the May 10, 2012 online edition ofthe Public Library of Science One. Study senior author, Neil Hayes, MD, MPH, associate professor ofmedicine, says, "It has been known for about a decade of usinggene expression arrays that "molecular subtypes" exist.These subtypes have molecular "fingerprints" andfrequently have different clinical outcomes. However, theunderlying etiologies of the subtypes have not been recognized. |
Whydo tumors form subtypes? "Our study shows that tumor subtypes have different underlyingalterations of DNA as part of the difference. These differences arefurther evidence of the importance of subtypes and the way we willuse them. For example, the mutations are different which may implymuch more ability to target than previously recognized. Also, weare starting to get a suggestion that these subtypes may reflectdifferent cells of origin that rely on different cancer pathways.This is further unlocking the diversity of this complexdisease." Hayes is a member of UNC Lineberger ComprehensiveCancer Center. The team first defined and reported in 2006 on three lung cancermolecular subtypes, named according to their genetic pattern --bronchoid, squamoid and magnoid.
In this PLoS One paper they sought to determine if distinct geneticmutations co-occur with each specific molecular subtypes. Theyfound that specific genetic mutations were associated with eachsubtype and that these mutations may have independent predictivevalue 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; LeighThorne, 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 SciencesCenter and Pittsburgh Cancer Institute. Funding for the study was provided by the National Cancer Instituteand the National Heart, Lung and Blood Institute, member institutesof the National Institutes of Health; Joan's Legacy Foundation; anda UNC Lineberger Clinical/Translational Developmental ResearchAward.
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