Translational Applications of Genomics
Neil Hayes, MD, MPH, University of Tennessee Health Science Center, Germantown, Tennessee, USA
Authored by Jason Willis, MD, PhD, University of Texas MD Anderson Cancer Center, Houston, Texas, USA
A multitude of large-scale genomic profiling studies have helped to define the landscape of somatic alterations in human cancers. The contribution of molecular diversity to variable clinical outcome (e.g. overall survival, treatment response, toxicity) has become the focus of intense study and is undoubtedly a critical component of personalized cancer medicine.
Towards this end, Dr. Hayes’ talk provided a valuable framework for young investigators to understand how translational genomic methods have been (and will continue to be) applied. The framework is centered on a common clinical question: how is patient outcome related to patient- and/or disease-specific features. Here, translational genomics plays an important role in allowing investigators to move beyond classic histopathologic disease features and characterize somatic alterations that may (1) reveal putative cells-of-origin; (2) define targets for novel drug development; or (3) identify prognostic or predictive biomarkers.
Dr. Hayes describes the example of glioblastoma multiforme, which has been classified into four molecular subtypes (proneural, neural, classical, and mesenchymal) on the basis of integrated mutation and gene expression profiling and unsupervised clustering. A further example is described in lung squamous cell carcinoma, where NRF2 mutations correlated with resistance to chemoradiation. This observation has led to the design of phase II biomarker study whereby early-stage patients with mutated/activated NRF2 are randomized to surgery, but wild-type NRF2 patients are randomized to chemoRT.
Throughout his talk, Dr. Hayes highlighted essential qualities for investigators that promote success in the field of translational genomics. First among these is the ability to work collaboratively and across disciplines as investigators build tissue biorepositories and analytical pipelines. Second is the recognition that genomic profiling is only the first step towards defining a novel and clinically-useful biomarker. It is important that genomic discoveries are placed within the context of existing clinical treatment paradigms.