To DNA or not to DNA? That Is the Question, When It Comes to Molecular Subtyping for the Clinic!

Genome-wide RNA expression profiling has yielded tumor subtypes with strong predictive or prognostic value for a wide variety of cancers. Recently, for breast cancer two RNA expression classifiers have been adopted by the World Health Organization (WHO) and approved by the Food and Drug Administration (FDA). Also on the basis of DNA copy number profiles, tumor subtypes with different prognosis have been described, but have not yet led to clinical implementation. The genomic revolution caused by next generation sequencing of DNA samples presents additional mutation, balanced translocations, single-nucleotide polymorphisms (SNP), and copy neutral loss of heterozygosity data simultaneously. We foresee a further boost of the potential of DNA profiling in the clinic when these multidimensional DNA factors will be implemented. Here we evaluate the current stratification power with DNA copy numbers. In a training and validation approach using data of 400 published breast cancer samples, we show that a DNA copy number classifier accurately classifies RNA expression subtypes. We consider this an important step forward for clinical implementation of genomic subtyping using DNA and discuss the extra dimensions upcoming techniques will bring to the DNA palette. Clin Cancer Res; 17(15); 4959-64. (C)2011 AACR.