Investigating the effect of 28 BRCA1 and BRCA2 mutations on their related transcribed mRNA

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• 作者：Francisco Quiles ; Mireia Menéndez ; Eva Tornero…
• 关键词：BRCA1 ; BRCA2 ; VUS ; Splicing ; RNA
• 刊名：Breast Cancer Research and Treatment
• 出版年：2016
• 出版时间：January 2016
• 年：2016
• 卷：155
• 期：2
• 页码：253-260
• 全文大小：1,091 KB
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• 作者单位：Francisco Quiles (1)
  Mireia Menéndez (1)
  Eva Tornero (1)
  Jesús del Valle (1)
  Àlex Teulé (1)
  Sarai Palanca (2)
  Angel Izquierdo (1)
  Carolina Gómez (1)
  Olga Campos (1)
  Raül Santamaria (3)
  Joan Brunet (1)
  Gabriel Capellá (1)
  Lídia Feliubadaló (1)
  Conxi Lázaro (1)
  
  1. Hereditary Cancer Program, Molecular Diagnostics Unit, Catalan Institute of Oncology (ICO-IDIBELL), Hospital Duran i Reynals, Gran Via 199, L’Hospitalet de Llobregat, 08908, Barcelona, Spain
  2. Molecular Biology Laboratory, Service of Clinical Analysis, University and Polytechnic Hospital La Fe, Valencia, Spain
  3. Genètica Molecular, Laboratorio Echevarne, Barcelona, Spain
  
• 刊物类别：Medicine
• 刊物主题：Medicine & Public Health
  Oncology
  
• 出版者：Springer Netherlands
• ISSN：1573-7217

文摘

Germline inactivating mutations in the BRCA1 and BRCA2 genes are responsible for hereditary breast and ovarian cancer syndrome (HBOCS). Genetic testing of these genes identifies a significant proportion of variants of uncertain significance (VUS). Elucidation of the clinical impact of these variants is an important challenge in genetic diagnostics and counseling. In this study, we assess the RNA effect of 28 BRCA1 and BRCA2 VUS identified in our set of HBOCS families with the aim of gaining insight into their clinical relevance. mRNA was extracted from VUS carriers and controls lymphocytes cultured for 5–6 days and treated with puromycin. RNA was reverse transcribed to perform transcriptional analysis for the study of splicing aberrations. In silico prediction tools were used to select those variants most likely to affect the RNA splicing process. Six out of the 28 variants analyzed showed an aberrant splicing pattern and could therefore be classified as probably pathogenic mutations. Reclassification of VUS improves the genetic counseling and clinical surveillance of carriers of these mutations and highlights the importance of RNA studies in routine diagnostic laboratories. Keywords BRCA1 BRCA2 VUS Splicing RNA