支票2
PALB2
遗传学
优先次序
RNA剪接
生物
基因
乳腺癌
基因检测
癌症
计算生物学
生物信息学
突变
种系突变
核糖核酸
经济
管理科学
作者
Verónica Castillo-Guardiola,Laura Rosado-Jiménez,MaDesamparados Sarabia-Meseguer,Miguel Marín-Vera,José Antonio Macías-Cerrolaza,Rosario García-Hernández,Marta Zafra-Poves,Pilar Sánchez-Henarejos,M.Á. Moreno-Locubiche,Encarnación Cuevas-Tortosa,María Arnaldos-Carrillo,Francisco Ayala de la Peña,José Luis Alonso-Romero,José Antonio Noguera-Velasco,Francisco Ruíz-Espejo
标识
DOI:10.1016/j.ejmg.2022.104468
摘要
BRCA1 and BRCA2 are the two main genes causing hereditary breast and ovarian cancer (HBOC). However, thanks to the development of Next Generation Sequencing (NGS), other genes linked to this syndrome (CHEK2, BRIP1, ATM and PALB2 among others) can be analysed.an analysis by multigene panel testing was performed in 138 index cases (ICs) from HBOC Spanish families with a previous non-informative result for BRCA1/2. The BRCA Hereditary Cancer Master™ Plus kit, including 26 actionable and candidate genes related to HBOC was employed. Once classified, an algorithm was employed to prioritized those variants of unknown significance with a higher risk of having a deleterious effect. Moreover, a mRNA splicing assay was performed for the prioritized VUS c.3402+3A > C in ATM, located at intron 23.A total of 82 variants were found: 70 VUS and 12 pathogenic or probably pathogenic variants. The diagnostic yield in actionable genes non-BRCA was 7.97% of the total tested ICs. Overall, 19 VUS were prioritized, which meant 27% of the 70 total VUS. RNA analysis of the variant 3402+3A > C confirmed a deleterious impact on splicing.The implementation of a multigene panel in HBOC studied families improved the diagnostic yield, concordant with results obtained in previous publications. Due to the important number of VUS obtained in NGS, the application of a prioritization algorithm is needed in order to select those variants in which it is necessary to conduct further studies.
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