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Management of familial cancer: sequencing, surveillance and society

Abstract

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.

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Figure 1: Evolution of clinical genetic screening for hereditary cancers.

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Acknowledgements

The work of the authors is supported in part by grants from the Canadian Institutes of Health Research (CIHR) to D.M. Both N.S. and A.V. receive salary support through scholarships from CIHR.

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All authors made substantial contributions to each stage of the preparation of the manuscript for submission. N.S. and A.V. contributed equally to the manuscript.

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Correspondence to David Malkin.

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Samuel, N., Villani, A., Fernandez, C. et al. Management of familial cancer: sequencing, surveillance and society. Nat Rev Clin Oncol 11, 723–731 (2014). https://doi.org/10.1038/nrclinonc.2014.169

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