The Kinghorn Cancer Centre and Cancer Division, Garvan Institute of Medical Research, Darlinghurst, NSW, Australia; Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, VIC, Australia; Research Division, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia.
Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, VIC, Australia; Familial Cancer Centre, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia.
Lancet Oncol. 2015 Jun;16(6):e303-8. doi: 10.1016/S1470-2045(15)70026-4. Epub 2015 May 27.
The study of human genetics has provided substantial insight into cancer biology. With an increase in sequencing capacity and a reduction in sequencing costs, genomics will probably transform clinical cancer genetics. A heritable basis for many cancers is accepted, but so far less than half the genetic drivers have been identified. Genomics will increasingly be applied to populations irrespective of family history, which will change the framework of phenotype-directed genetic testing. Panel testing and whole genome sequencing will identify novel, polygenic, and de-novo determinants of cancer risk, often with lower penetrance, which will challenge present binary clinical classification systems and management algorithms. In the future, genotype-stratified public screening and prevention programmes could form part of tailored population risk management. The integration of research with clinical practice will result in so-called discovery cohorts that will help identify clinically significant genetic variation.
人类遗传学研究为癌症生物学提供了重要的见解。随着测序能力的提高和测序成本的降低，基因组学可能会改变临床癌症遗传学。人们已经接受了许多癌症的遗传性基础，但到目前为止，只有不到一半的遗传驱动因素被确定。基因组学将越来越多地应用于没有家族史的人群，这将改变基于表型的遗传检测的框架。面板测试和全基因组测序将确定癌症风险的新的、多基因的和新生的决定因素，这些因素通常具有较低的外显率，这将挑战目前的二元临床分类系统和管理算法。在未来，基于基因型的公众筛查和预防计划可能成为定制人群风险管理的一部分。研究与临床实践的结合将产生所谓的发现队列，这将有助于确定具有临床意义的遗传变异。
