Advanced

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

Ratajska, Magdalena; Krygier, Magdalena; Stukan, Maciej; Kuzniacka, Alina; Koczkowska, Magdalena; Dudziak, Miroslaw; Sniadecki, Marcin; Debniak, Jaroslaw; Wydra, Dariusz and Brozek, Izabela, et al. (2015) In Journal of Applied Genetics 56(2). p.193-198
Abstract
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 = 13) 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... (More)
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 = 13) 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 = 5/12; 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. (Less)
Please use this url to cite or link to this publication:
author
, et al. (More)
(Less)
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
BRCA1, BRCA2, Mutations, Next generation sequencing, Ovarian cancer, PARP inhibitors
in
Journal of Applied Genetics
volume
56
issue
2
pages
193 - 198
publisher
Springer
external identifiers
  • wos:000353212900006
  • scopus:84939969051
ISSN
1234-1983
DOI
10.1007/s13353-014-0254-5
language
English
LU publication?
yes
id
21c2251c-1354-406a-bb29-d59cb8bacb83 (old id 5386106)
date added to LUP
2015-06-01 09:26:04
date last changed
2017-01-22 03:52:41
@article{21c2251c-1354-406a-bb29-d59cb8bacb83,
  abstract     = {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 = 13) 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 = 5/12; 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.},
  author       = {Ratajska, Magdalena and Krygier, Magdalena and Stukan, Maciej and Kuzniacka, Alina and Koczkowska, Magdalena and Dudziak, Miroslaw and Sniadecki, Marcin and Debniak, Jaroslaw and Wydra, Dariusz and Brozek, Izabela and Biernat, Wojciech and Borg, Åke and Limon, Janusz and Wasag, Bartosz},
  issn         = {1234-1983},
  keyword      = {BRCA1,BRCA2,Mutations,Next generation sequencing,Ovarian cancer,PARP inhibitors},
  language     = {eng},
  number       = {2},
  pages        = {193--198},
  publisher    = {Springer},
  series       = {Journal of Applied Genetics},
  title        = {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},
  url          = {http://dx.doi.org/10.1007/s13353-014-0254-5},
  volume       = {56},
  year         = {2015},
}