Clinical Utility of Functional RNA Analysis for the Reclassification of Splicing Gene Variants in Hereditary Cancer

Overview

Journal Cancer Genomics Proteomics

Specialties Biochemistry
Genetics
Oncology

Date 2021 Apr 24

PMID 33893081

Citations 7

Authors

Konstantinos Agiannitopoulos

Georgia Pepe

Eirini Papadopoulou

Georgios N Tsaousis

Stavroula Kampouri

Sonia Maravelaki

Athanassios Fassas

Christos Christodoulou

Rodoniki Iosifidou

Sofia Karageorgopoulou

Christos Markopoulos

Ioannis Natsiopoulos

Konstantinos Papazisis

Maria Vasilaki-Antonatou

Vassileios Venizelos

Vahit Ozmen

Sualp Tansan

Kerim Kaban

Dan Tudor Eniu

Angelica Chiorean

George Nasioulas

Affiliations

Soon will be listed here.

Abstract

Background: Classification of splicing variants (SVs) in genes associated with hereditary cancer is often challenging. The aim of this study was to investigate the occurrence of SVs in hereditary cancer genes and the clinical utility of RNA analysis.

Material And Methods: 1518 individuals were tested for cancer predisposition, using a Next Generation Sequencing (NGS) panel of 36 genes. Splicing variant analysis was performed using RT-PCR and Sanger Sequencing.

Results: In total, 34 different SVs were identified, 53% of which were classified as pathogenic or likely pathogenic. The remaining 16 variants were initially classified as Variant of Uncertain Significance (VUS). RNA analysis was performed for 3 novel variants.

Conclusion: The RNA analysis assisted in the reclassification of 20% of splicing variants from VUS to pathogenic. RNA analysis is essential in the case of uncharacterized splicing variants, for proper classification and personalized management of these patients.

Citing Articles

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Diagnostic Outcomes of Concurrent DNA and RNA Sequencing in Individuals Undergoing Hereditary Cancer Testing.

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