Translational genomics in breast cancer

摘要: The six biological characteristics acquired by cells during the multistep development of human cancers are well defined (sustaining proliferative signalling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, and activating invasion metastasis) result from accumulation mutations [1]. To this “cell autonomous”-centric view tumour microenvironment, modulated host genome, is increasingly recognised as much more than a bystander, since it contributes to properties Under conceptual framework complete characterisation germline genomes should provide us with all information for better managing cancer patients [2]. Until goal reached research needed demonstrate that will be clinically useful. date most in breast (and other cancers) has used technology falls short providing true whole genome relied on microarrays DNA/RNA, targeted mutational analysis, or tissue-based proteins nucleic acids [3,4]. Sequencing progressed rapidly, allowing at single nucleotide resolution DNA RNA, first example showing enormous complexity evolution between primary distant metastasis [5]. A large international effort underway, characterising thousands genomes, including (eventually) around 2000 cancers, which represent gigantic step understanding extent how affect plans its application clinical setting [6]. Even continually improving sequencing decreasing costs take years investment before we have evidence (germline polymorphisms somatic mutations) knowledge then translate into improved screening, diagnosis, prognostication, prediction, treatments response monitoring. All early would suggest case, and, example, drugs treatment strategies being developed based molecular tumours [7]. There also increasing classifiers prognostication can derived combined analysis profile both RNA [8–10]. validation “first-generation” prognostic signatures, usually exclusively gene expression profiling, proven particularly challenging [11]. It been even difficult identify validate predictors nontargeted therapies (radiotherapy chemotherapy), although sample sets trials already provided preliminary novel markers [12]. Neoadjuvant therapy hold great promise right these predictive biomarkers chemotherapy therapies) response. ER Her2 lack benefit (hormone anti-Her2-targeted agents) when do not express (i.e. excellent negative value), but fail despite expressing still respond therapies. Again there fully underlie mechanisms resistance [13]. next couple see reporting results several studies glimpses where field going. These include study array-based profiling an Anglo-Canadian consortium (METABRIC), genomic few hundreds groups Europe, Canada USA, context neoadjuvant studies. In future patient samples, pre-requisite determining utility ultimately strategy improve management delivering personalised medicine.