Germline mutation screening of the Saethre-Chotzen-associated genes TWIST1 and FGFR3 in families with BRCA1/2-negative breast cancer

Annika Bergman; Pelle Sahlin; Monica Emanuelsson; Helena Carén; Peter Tarnow; Tommy Martinsson; Henrik Grönberg; Göran Stenman

doi:10.3109/02844310903247228

Germline mutation screening of the Saethre-Chotzen-associated genes TWIST1 and FGFR3 in families with BRCA1/2-negative breast cancer

Scand J Plast Reconstr Surg Hand Surg. 2009;43(5):251-5. doi: 10.3109/02844310903247228.

Authors

Annika Bergman¹, Pelle Sahlin, Monica Emanuelsson, Helena Carén, Peter Tarnow, Tommy Martinsson, Henrik Grönberg, Göran Stenman

Affiliation

¹ Lundberg Laboratory for Cancer Research, Department of Pathology, The Sahlgrenska Academy at the University of Gothenburg, Sahlgrenska University Hospital, Göteborg, Sweden.

PMID: 19863427
DOI: 10.3109/02844310903247228

Abstract

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Acrocephalosyndactylia / epidemiology
Acrocephalosyndactylia / genetics*
Adult
Breast Neoplasms / epidemiology
Breast Neoplasms / genetics
Core Binding Factor Alpha 1 Subunit / genetics
DNA-Binding Proteins / genetics
Ephrin-B1 / genetics
Female
Genes, BRCA1
Genes, BRCA2
Genetic Testing*
Germ-Line Mutation*
Homeodomain Proteins / genetics
Humans
Middle Aged
Nuclear Proteins / genetics*
Polymerase Chain Reaction
Receptor, Fibroblast Growth Factor, Type 1 / genetics
Receptor, Fibroblast Growth Factor, Type 2 / genetics
Receptor, Fibroblast Growth Factor, Type 3 / genetics*
Receptor, Fibroblast Growth Factor, Type 4 / genetics
Sequence Analysis, DNA
Transcription Factors / genetics
Twist-Related Protein 1 / genetics*

Substances

ALX4 protein, human
Core Binding Factor Alpha 1 Subunit
DNA-Binding Proteins
EFNB1 protein, human
Ephrin-B1
Homeodomain Proteins
MSX2 protein
Nuclear Proteins
RUNX2 protein, human
TWIST1 protein, human
Transcription Factors
Twist-Related Protein 1
FGFR1 protein, human
FGFR2 protein, human
FGFR3 protein, human
FGFR4 protein, human
Receptor, Fibroblast Growth Factor, Type 1
Receptor, Fibroblast Growth Factor, Type 2
Receptor, Fibroblast Growth Factor, Type 3
Receptor, Fibroblast Growth Factor, Type 4