Informace o publikaci
Improving the Diagnostic Yield of Genetic Testing for Hereditary Cancer Syndromes with RNA Sequencing
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| Rok publikování | 2023 |
| Druh | Konferenční abstrakty |
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| Popis | Background: Next-generation DNA sequencing has become the gold standard for genetic testing. However, this technique is accompanied by several technical limitations, including the failure to effectively detect hidden splice-site variants which might account for a significant part of potentially deleterious variants implicated in hereditary cancers. In this project, we focus on this significant diagnostic gap, aiming to enhance the sensitivity and specificity of genetic testing by integrating RNA sequencing into the established DNA sequencing protocols. The objective is not only to identify novel, clinically relevant, transcript-altering pathogenic variants but also to re-evaluate and possibly reclassify variants of unknown significance (VUS), thereby facilitating more precise risk assessment and personalized patient management. Patients and methods: Patients that have met the criteria for genetic testing and that have been previously found to carry a splice-site variant of unknown significance using DNA sequencing and splice prediction tools have been selected. The RNA isolation from whole blood has been performed using three commercially available kits in order to maximize the RNA yield, followed by targeted RNA capture and sequencing of the 226 genes included in the CZECANCA panel. Results: So far, 40 patients have been analyzed. We have confirmed the suspected aberrant splicing for several previously unreported potentially pathogenic variants in several genes (e. g. ATM, MHS2 and BRCA2) and have been able to describe the effect of abnormal mRNA transcripts for variants with previously unavailable RNAseq data. Conclusion: While our laboratory is still in the process of establishing RNA sequencing as a routine diagnostic tool adjunct to conventional DNA sequencing, it is already evident that this method can increase the diagnostic yield of genetic testing. More accurate diagnosis translates into more effective preventive measures, early detection strategies, and personalized treatment approaches, thereby improving clinical outcomes for patients and their relatives. |