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Title:Identification of spliceogenic variants beyond canonical GT-AG splice sites in hereditary cancer genes
Authors:ID Šetrajčič Dragoš, Vita (Author)
ID Strojnik, Ksenija (Author)
ID Klančar, Gašper (Author)
ID Škerl, Petra (Author)
ID Stegel, Vida (Author)
ID Blatnik, Ana (Author)
ID Banjac, Marta (Author)
ID Krajc, Mateja (Author)
ID Novaković, Srdjan (Author)
Files:URL URL - Source URL, visit https://www.mdpi.com/1422-0067/23/13/7446
 
.pdf PDF - Presentation file, download (778,18 KB)
MD5: 474DFF0799FF629B33541DF287F153D6
 
Language:English
Typology:1.01 - Original Scientific Article
Organization:Logo OI - Institute of Oncology
Abstract:Pathogenic/likely pathogenic variants in susceptibility genes that interrupt RNA splicing are a well-documented mechanism of hereditary cancer syndromes development. However, if RNA studies are not performed, most of the variants beyond the canonical GT-AG splice site are characterized as variants of uncertain significance (VUS). To decrease the VUS burden, we have bioinformatically evaluated all novel VUS detected in 732 consecutive patients tested in the routine genetic counseling process. Twelve VUS that were predicted to cause splicing defects were selected for mRNA analysis. Here, we report a functional characterization of 12 variants located beyond the first two intronic nucleotides using RNAseq in APC, ATM, FH, LZTR1, MSH6, PALB2, RAD51C, and TP53 genes. Based on the analysis of mRNA, we have successfully reclassified 50% of investigated variants. 25% of variants were downgraded to likely benign, whereas 25% were upgraded to likely pathogenic leading to improved clinical management of the patient and the family members.
Keywords:hereditary cancer, RNA sequencing, spliceogenic
Publication status:Published
Publication version:Version of Record
Publication date:04.07.2022
Publisher:MDPI
Year of publishing:2022
Number of pages:str. 7446-1-7446-14
Numbering:Vol. 23, no. 13
PID:20.500.12556/DiRROS-15458 New window
UDC:602
ISSN on article:1422-0067
DOI:10.3390/ijms23137446 New window
COBISS.SI-ID:114023427 New window
Copyright:by Authors
Note:Nasl. z nasl. zaslona; Opis vira z dne 6. 7. 2022;
Publication date in DiRROS:07.09.2022
Views:446
Downloads:231
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Record is a part of a journal

Title:International journal of molecular sciences
Shortened title:Int. j. mol. sci.
Publisher:MDPI
ISSN:1422-0067
COBISS.SI-ID:2779162 New window

Document is financed by a project

Funder:ARRS - Slovenian Research Agency
Project number:P3-0352-2018
Name:Družine s povišano ali visoko ogroženostjo za raka: svetovanje, odkrivanje mutacij in preprečevanje raka

Licences

License:CC BY 4.0, Creative Commons Attribution 4.0 International
Link:http://creativecommons.org/licenses/by/4.0/
Description:This is the standard Creative Commons license that gives others maximum freedom to do what they want with the work as long as they credit the author.
Licensing start date:07.09.2022

Secondary language

Language:Slovenian
Keywords:dedni raki, sekvencioniranje RNA, spajanje, geni


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