Germline mutation screening of the Saethre-Chotzen-associated genes TWIST1 and FGFR3 in families with BRCA1/2-negative breast cancer.
Saethre-Chotzen syndrome is one of the most common craniosynostosis syndromes. It is an autosomal dominantly inherited disorder with variable expression that is caused by germline mutations in the TWIST1 gene or more rarely in the FGFR2 or FGFR3 genes. We have previously reported that patients with Saethre-Chotzen syndrome have an increased risk of developing breast cancer. Here we have analysed a cohort of 26 women with BRCA1/2-negative hereditary breast cancer to study whether a proportion of these families might have mutations in Saethre-Chotzen-associated genes. DNA sequence analysis of TWIST1 showed no pathogenic mutations in the coding sequence in any of the 26 patients. MLPA (multiplex ligation-dependent probe amplification)-analysis also showed no alterations in copy numbers in any of the craniofacial disorder genes MSX2, ALX4, RUNX2, EFNB1, TWIST1, FGFR1, FGFR2,FGFR3, or FGFR4. Taken together, our findings indicate that mutations in Saethre-Chotzen-associated genes are uncommon or absent in BRCA1/2-negative patients with hereditary breast cancer.
Lundberg Laboratory for Cancer Research, Department of Pathology, The Sahlgrenska Academy at the University of Gothenburg, Sahlgrenska University Hospital, Göteborg, Sweden.
Annika
A
Bergman
Pelle
P
Sahlin
Monica
M
Emanuelsson
Helena
H
Carén
Peter
P
Tarnow
Tommy
T
Martinsson
Henrik
H
Grönberg
Göran
G
Stenman
D000168:Acrocephalosyndactylia / Q000453:epidemiology / Q000235:genetics*; D000328:Adult; D001943:Breast Neoplasms / Q000453:epidemiology / Q000235:genetics; D050659:Core Binding Factor Alpha 1 Subunit / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics; D036387:Ephrin-B1 / Q000235:genetics; D005260:Female; D019398:Genes, BRCA1; D024522:Genes, BRCA2; D005820:Genetic Testing; D018095:Germ-Line Mutation; D018398:Homeodomain Proteins / Q000235:genetics; D006801:Humans; D008875:Middle Aged; D009687:Nuclear Proteins / Q000235:genetics*; D016133:Polymerase Chain Reaction; D051496:Receptor, Fibroblast Growth Factor, Type 1 / Q000235:genetics; D051497:Receptor, Fibroblast Growth Factor, Type 2 / Q000235:genetics; D051498:Receptor, Fibroblast Growth Factor, Type 3 / Q000235:genetics*; D051499:Receptor, Fibroblast Growth Factor, Type 4 / Q000235:genetics; D017422:Sequence Analysis, DNA; D014157:Transcription Factors / Q000235:genetics; D051879:Twist-Related Protein 1 / Q000235:genetics*
C416676:ALX4 protein, human; D050659:Core Binding Factor Alpha 1 Subunit; D004268:DNA-Binding Proteins; C484288:EFNB1 protein, human; D036387:Ephrin-B1; D018398:Homeodomain Proteins; C084119:MSX2 protein; D009687:Nuclear Proteins; C493709:RUNX2 protein, human; C103173:TWIST1 protein, human; D014157:Transcription Factors; D051879:Twist-Related Protein 1; C496348:FGFR1 protein, human; C496353:FGFR2 protein, human; C496365:FGFR3 protein, human; C496371:FGFR4 protein, human; D051496:Receptor, Fibroblast Growth Factor, Type 1; D051497:Receptor, Fibroblast Growth Factor, Type 2; D051498:Receptor, Fibroblast Growth Factor, Type 3; D051499:Receptor, Fibroblast Growth Factor, Type 4