title: Mutation analysis of BRCA1, BRCA2, PALB2 and BRD7 in a hospital-based series of German patients with triple-negative breast cancer.
abstract: Triple-negative breast cancer (TNBC) is an aggressive form of breast carcinoma with a poor prognosis. Recent evidence suggests that some patients with TNBC harbour germ-line mutations in DNA repair genes which may render their tumours susceptible to novel therapies such as treatment with PARP inhibitors. In the present study, we have investigated a hospital-based series of 40 German patients with TNBC for the presence of germ-line mutations in BRCA1, BRCA2, PALB2, and BRD7 genes. Microfluidic array PCR and next-generation sequencing was used for BRCA1 and BRCA2 analysis while conventional high-resolution melting and Sanger sequencing was applied to study the coding regions of PALB2 and BRD7, respectively. Truncating mutations in BRCA1 were found in six patients, and truncating mutations in BRCA2 and PALB2 were detected in one patient each, whereas no truncating mutation was identified in BRD7. One patient was a double heterozygote for the PALB2 mutation, c.758insT, and a BRCA1 mutation, c.927delA. Our results confirm in a hospital-based setting that a substantial proportion of German TNBC patients (17.5%) harbour germ-line mutations in genes involved in homology-directed DNA repair, with a preponderance of BRCA1 mutations. Triple-negative breast cancer should be considered as an additional criterion for future genetic counselling and diagnostic sequencing.
authors.affiliation: Clinics of Obstetrics and Gynaecology, Hannover Medical School, Hannover, Germany.
authors.forename: Franziska
authors.initials: F
authors.lastname: Pern
authors.forename: Natalia
authors.initials: N
authors.lastname: Bogdanova
authors.forename: Peter
authors.initials: P
authors.lastname: Schürmann
authors.forename: Min
authors.initials: M
authors.lastname: Lin
authors.forename: Aysun
authors.initials: A
authors.lastname: Ay
authors.forename: Florian
authors.initials: F
authors.lastname: Länger
authors.forename: Peter
authors.initials: P
authors.lastname: Hillemanns
authors.forename: Hans
authors.initials: H
authors.lastname: Christiansen
authors.forename: Tjoung-Won
authors.initials: TW
authors.lastname: Park-Simon
authors.forename: Thilo
authors.initials: T
authors.lastname: Dörk
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D019313:BRCA1 Protein; D024682:BRCA2 Protein; D001483:Base Sequence; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D002868:Chromosomal Proteins, Non-Histone; D004252:DNA Mutational Analysis / Q000379:methods; D000076164:Fanconi Anemia Complementation Group N Protein; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D018095:Germ-Line Mutation; D005858:Germany; D006801:Humans; D008875:Middle Aged; D009687:Nuclear Proteins; D009775:Obstetrics and Gynecology Department, Hospital / Q000706:statistics & numerical data; D016133:Polymerase Chain Reaction / Q000379:methods; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics / Q000378:metabolism; D011960:Receptors, Estrogen / Q000235:genetics / Q000378:metabolism; D011980:Receptors, Progesterone / Q000235:genetics / Q000378:metabolism; D025521:Tumor Suppressor Proteins; D055815:Young Adult; D000092468:Bromodomain Containing Proteins
chemical_list: D019313:BRCA1 Protein; D024682:BRCA2 Protein; D002868:Chromosomal Proteins, Non-Histone; D000076164:Fanconi Anemia Complementation Group N Protein; D009687:Nuclear Proteins; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D025521:Tumor Suppressor Proteins; C485694:BRD7 protein, human; D000092468:Bromodomain Containing Proteins; C512790:PALB2 protein, human