Translating genomics to the clinic: implications of cancer heterogeneity.

BACKGROUND: Sequencing of cancer genomes has become a pivotal method for uncovering and understanding the deregulated cellular processes driving tumor initiation and progression. Whole-genome sequencing is evolving toward becoming less costly and more feasible on a large scale; consequently, thousands of tumors are being analyzed with these technologies. Interpreting these data in the context of tumor complexity poses a challenge for cancer genomics. CONTENT: The sequencing of large numbers of tumors has revealed novel insights into oncogenic mechanisms. In particular, we highlight the remarkable insight into the pathogenesis of breast cancers that has been gained through comprehensive and integrated sequencing analysis. The analysis and interpretation of sequencing data, however, must be considered in the context of heterogeneity within and among tumor samples. Only by adequately accounting for the underlying complexity of cancer genomes will the potential of genome sequencing be understood and subsequently translated into improved management of patients.
SUMMARY: The paradigm of personalized medicine holds promise if patient tumors are thoroughly studied as unique and heterogeneous entities and clinical decisions are made accordingly. Associated challenges will be ameliorated by continued collaborative efforts among research centers that coordinate the sharing of mutation, intervention, and outcomes data to assist in the interpretation of genomic data and to support clinical decision-making.