Authors: J. Soukupová 1; P. Zemánková 1; P. Kleiblová 1,2; M. Janatová 1; Z. Kleibl 1 Authors‘ workplace: Ústav biochemie a experimentální onkologie, 1. LF UK v Praze 1; Ústav biologie a lékařské genetiky, 1. LF UK a VFN v Praze 2 Published in: Klin Onkol 2016; 29(Supplementum 1): 46-54 Category: Original Articles doi: https://doi.org/10.14735/amko2016S46
Individuals with hereditary cancer syndromes form a minor but clinically important subgroup of oncology patients, comprising several thousand cases in the Czech Republic annually. In these patients, the identification of pathogenic mutations in cancer susceptibility genes has an important predictive and, in some cases, prognostic value. It also enables rational preventive strategies in asymptomatic carriers from affected families. More than 150 cancer susceptibility genes have been described so far; however, mutations in most of them are very rare, occurring with substantial population variability, and hence their clinical interpretation is very complicated. Diagnostics of mutations in cancer susceptibility genes have benefited from the broad availability of next-generation sequencing analyses using targeted gene panels. In order to rationalize the diagnostics of hereditary cancer syndromes in the Czech Republic, we have prepared the sequence capture panel “CZECANCA”, targeting 219 cancer susceptibility genes. Besides more than 50 clinically important high - and moderate-penetrance susceptibility genes, the panel also targets less common candidate genes with uncertain clinical relevance. Alongside the panel design, we have optimized the analytical and bioinformatics pipeline, which will facilitate establishing a collective nationwide database of genotypes and clinical data from the analyzed individuals. The key objective of this project is to provide diagnostic laboratories in the Czech Republic with a reliable procedure and collective database improving the clinical utility of next-generation sequencing analyses in high-risk patients, which would help improve the interpretation of rare or population-specific variants in cancer susceptibility genes.
Key words: genetic predisposition testing – hereditary cancer syndromes – high-throughput nucleotide sequencing – genetic information databases – panel sequencing – sequence capture – next-generation sequencing (NGS) This work was supported by Czech Ministry of Health grants No. NT14054, NV15-28830A, NV15--27695A and The League Against Cancer Prague. The authors declare they have no potential conflicts of interest concerning drugs, products, or services used in the study. The Editorial Board declares that the manuscript met the ICMJE recommendation for biomedical papers.
Submitted: 2. 10. 2015
Accepted: 13. 10. 2015
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