Department of Medical Biophysics, University of Toronto, Division of Hematology/Oncology and Genetics &Genome Biology Program, The Hospital for Sick Children, 555 University Avenue, Toronto, ON M5G 1X8, Canada.
Department of Pediatrics and Institute of Medical Science, University of Toronto, Division of Hematology/Oncology and Genetics &Genome Biology Program, The Hospital for Sick Children, 555 University Avenue, Toronto, ON M5G 1X8, Canada.
Nat Rev Clin Oncol. 2014 Dec;11(12):723-31. doi: 10.1038/nrclinonc.2014.169. Epub 2014 Oct 14.
The clinical management of familial cancer begins with recognition of patterns of cancer occurrence suggestive of genetic susceptibility in a proband or pedigree, to enable subsequent investigation of the underlying DNA mutations. In this regard, next-generation sequencing of DNA continues to transform cancer diagnostics, by enabling screening for cancer-susceptibility genes in the context of known and emerging familial cancer syndromes. Increasingly, not only are candidate cancer genes sequenced, but also entire 'healthy' genomes are mapped in children with cancer and their family members. Although large-scale genomic analysis is considered intrinsic to the success of cancer research and discovery, a number of accompanying ethical and technical issues must be addressed before this approach can be adopted widely in personalized therapy. In this Perspectives article, we describe our views on how the emergence of new sequencing technologies and cancer surveillance strategies is altering the framework for the clinical management of hereditary cancer. Genetic counselling and disclosure issues are discussed, and strategies for approaching ethical dilemmas are proposed.
家族性癌症的临床管理始于对先证者或家系中提示遗传易感性的癌症发生模式的识别，以便随后对潜在的 DNA 突变进行调查。在这方面，DNA 的下一代测序通过在已知和新兴的家族性癌症综合征背景下筛选癌症易感基因，继续改变癌症诊断。越来越多的不仅是候选癌症基因被测序，而且在患有癌症的儿童及其家庭成员中还绘制了整个“健康”基因组。尽管大规模基因组分析被认为是癌症研究和发现成功的内在因素，但在这种方法可以广泛应用于个性化治疗之前，必须解决一些伴随的伦理和技术问题。在这篇观点文章中，我们描述了我们对新测序技术和癌症监测策略的出现如何改变遗传性癌症临床管理框架的看法。讨论了遗传咨询和披露问题，并提出了解决伦理困境的策略。
