Mutational analysis of BRCA1/2 in a group of 134 consecutive ovarian cancer patients. Novel and recurrent BRCA1/2 alterations detected by next generation sequencing

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• 作者：Magdalena Ratajska ; Magdalena Krygier ; Maciej Stukan…
• 关键词：BRCA1 ; BRCA2 ; Mutations ; Next generation sequencing ; Ovarian cancer ; PARP inhibitors
• 刊名：Journal of Applied Genetics
• 出版年：2015
• 出版时间：May 2015
• 年：2015
• 卷：56
• 期：2
• 页码：193-198
• 全文大小：169 KB
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• 作者单位：Magdalena Ratajska (1)
  Magdalena Krygier (1)
  Maciej Stukan (2)
  Alina Ku?niacka (1)
  Magdalena Koczkowska (1)
  Miros?aw Dudziak (2)
  Marcin ?niadecki (3)
  Jaros?aw D?bniak (3)
  Dariusz Wydra (3)
  Izabela Brozek (1)
  Wojciech Biernat (4)
  Ake Borg (5)
  Janusz Limon (1)
  Bartosz Was?g (1)
  
  1. Department of Biology and Genetics, Medical University of Gdansk, Debinki 1, 80-210, Gdansk, Poland
  2. Department of Gynecologic Oncology, Gdynia Oncology Center, Gdynia, Poland
  3. Department of Gynaecology, Gynaecological Oncology and Gynaecological Endocrinology, Medical University of Gdansk, Gdansk, Poland
  4. Department of Pathomorphology, Medical University of Gdansk, Gdansk, Poland
  5. Department of Oncology, CREATE Health Strategic Center for Translational Cancer Research, Skane Department of Oncology, Lund University, Skane University Hospital, Lund, Sweden
  
• 刊物主题：Life Sciences, general; Animal Genetics and Genomics; Human Genetics; Microbial Genetics and Genomics; Plant Genetics & Genomics;
• 出版者：Springer Berlin Heidelberg
• ISSN：2190-3883

文摘

The importance of proper mutational analysis of BRCA1/2 in individuals at risk for hereditary breast and ovarian cancer syndrome is widely accepted. Standard genetic screening includes targeted analysis of recurrent, population-specific mutations. The purpose of the study was to establish the frequency of germline BRCA1/2 mutations in a group of 134 unrelated patients with primary ovarian cancer. Next generation sequencing analysis revealed a presence of 20 (14.9?%) mutations, where 65?% (n--3) were recurrent BRCA1 alterations included in the standard diagnostic panel in northern Poland. However, the remaining seven BRCA1/2 mutations (35?%) would be missed by the standard approach and were detected in unique patients. A substantial proportion (n--/12; 41?%) of mutation-positive individuals with complete family history reported no incidence of breast or ovarian cancer in their relatives. This observation, together with the raising perspectives for personalized therapy targeting BRCA1/2 signaling pathways indicates the necessity of comprehensive genetic screening in all ovarian cancer patients. However, due to the limited sensitivity of the standard genetic screening presented in this study (65?%) an application of next generation sequencing in molecular diagnostics of BRCA1/2 genes should be considered.