title: New recurrent BRCA1/2 mutations in Polish patients with familial breast/ovarian cancer detected by next generation sequencing.
abstract: BACKGROUND
  Targeted PCR-based genetic testing for BRCA1 and BRCA2 can be performed at a lower cost than full gene testing; however, it may overlook mutations responsible for familial breast and/or ovarian cancers. In the present study, we report the utility of next generation sequencing (NGS) to identify new pathogenic variants of BRCA1/2.
  
  
  METHODS
  BRCA1 and BRCA2 exons were amplified using the Ion AmpliSeq BRCA1/2 Panel and sequenced on the Ion Torrent PGM sequencer in 512 women with familial and/or only early onset breast and/or ovarian cancers who were negative for selected BRCA1/2 mutations.
  
  
  RESULTS
  146 single nucleotide variants (SNVs) and 32 indels were identified. Of them, 14 SNVs and 17 indels were considered as pathogenic or likely pathogenic. One and 18 pathogenic mutations had been detected previously in the Polish and other populations, respectively, and 12 deleterious mutations were previously unknown. Eight mutations were recurrent; Q563X (BRCA1), N3124I (BRCA2) and c.4516delG (BRCA1) were found in eight, six and four patients, respectively, and two other mutations (c.9118-2A > G and c.7249delCA in BRCA2) were detected in three patients each. Altogether, BRCA1/2 pathogenic mutations were identified in 52 out of 512 (10%) patients.
  
  
  CONCLUSIONS
  NGS substantially improved the detection rates of a wide spectrum of mutations in Polish patients with familial breast and/or ovarian cancer. Although targeted screening for specific BRCA1 mutations can be offered to all Polish breast or ovarian cancer patients, NGS-based testing is justified in patients with breast or ovarian cancer likely related to BRCA1/2 who test negative for the selected BRCA1/2 pathogenic mutations.
authors.affiliation: Department of Genetics, Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, 02-781, Warsaw, Poland. akluska@coi.waw.pl.
authors.forename: Anna
authors.initials: A
authors.lastname: Kluska
authors.affiliation: Department of Genetics, Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, 02-781, Warsaw, Poland. abalabas@coi.waw.pl.
authors.forename: Aneta
authors.initials: A
authors.lastname: Balabas
authors.affiliation: Department of Gastroenterology, Hepatology and Clinical Oncology, Medical Center for Postgraduate Education, 01-813, Warsaw, Poland. agapaziewska@poczta.onet.pl.
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Paziewska
authors.affiliation: Department of Gastroenterology, Hepatology and Clinical Oncology, Medical Center for Postgraduate Education, 01-813, Warsaw, Poland. mkulecka@cmkp.edu.pl.
authors.forename: Maria
authors.initials: M
authors.lastname: Kulecka
authors.affiliation: Department of Genetics, Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, 02-781, Warsaw, Poland. donow@coi.waw.pl.
authors.forename: Dorota
authors.initials: D
authors.lastname: Nowakowska
authors.affiliation: Department of Genetics, Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, 02-781, Warsaw, Poland. mikula.michal@gmail.com.
authors.forename: Michal
authors.initials: M
authors.lastname: Mikula
authors.affiliation: Department of Genetics, Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, 02-781, Warsaw, Poland. jostrow@warman.com.pl.|Department of Gastroenterology, Hepatology and Clinical Oncology, Medical Center for Postgraduate Education, 01-813, Warsaw, Poland. jostrow@warman.com.pl.
authors.forename: Jerzy
authors.initials: J
authors.lastname: Ostrowski
mesh_terms: D000328:Adult; D000368:Aged; D019313:BRCA1 Protein / Q000235:genetics*; D024682:BRCA2 Protein / Q000235:genetics*; D001943:Breast Neoplasms / Q000235:genetics*; D004252:DNA Mutational Analysis; D005091:Exons; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D007477:Ions; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009369:Neoplasms / Q000235:genetics / Q000378:metabolism; D010051:Ovarian Neoplasms / Q000235:genetics*; D011044:Poland; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide
chemical_list: D019313:BRCA1 Protein; C492913:BRCA1 protein, human; D024682:BRCA2 Protein; C551750:BRCA2 protein, human; D007477:Ions