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Next-generation sequencing in breast cancer: translational science and clinical integration.

Since the unveiling of the first draft human genome in 2001 [1,2], there has been a rapid development of technologies that can sequence entire human genomes, transcriptomes and methylomes in an expedient and cost-effective manner [3]. The current suite of technologies, known collectively as next-generation sequencing (NGS), has ushered in an exciting era of genomics research that has precipitated the democratization of large-scale sequencing from genome centers to individual laboratories. In particular, NGS has revolutionized how genes are studied in malignancies by providing single nucleotide resolution to detect a variety of mutations, measure differential gene expression, and determine methylation states on a genome-wide scale [4]. Since the sequencing of the first cancer genome [5], there has been a rapid production of cancer sequencing data, most notably demonstrated by the efforts of major consortia such as The Cancer Genome Atlas and the International Cancer Genome Consortium [6]. These groups are actively sequencing tens of thousands of cancer genomes and transcriptomes and have already reported a variety of recurrently mutated genes and pathways with therapeutic implications. NGS continues to make headway in cancer research by discovering disease-causing mutations, identifying novel drug targets and implementing therapeutic individualization. One arena where NGS is making great strides in translational research is in the study of breast cancer. This was first demonstrated by seminal work at the Wellcome Trust Sanger Institute (Cambridge, UK) where the use of NGS revealed a diverse spectrum of somatic rearrangements in breast cancer [7]. This work reported that breast cancers contain a plethora of rearrangements including: tandem duplications, interand intra-chromosomal gene fusions, deletions