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.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Kirurgi (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Surgery (hsv//eng)

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Cancer och onkologi (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Cancer and Oncology (hsv//eng)

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Cell- och molekylärbiologi (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Cell and Molecular Biology (hsv//eng)

Nyckelord

BRCA1

BRCA2

FGFR2

FGFR3

Hereditary breast cancer

Saethre-Chotzen syndrome

TWIST1

ALX4 protein

human

DNA binding protein

EFNB1 protein

human

ephrin B1

FGFR1 protein

human

FGFR2 protein

human

FGFR3 protein

human

FGFR4 protein

human

fibroblast growth factor receptor 1

fibroblast growth factor receptor 2

fibroblast growth factor receptor 3

fibroblast growth factor receptor 4

homeodomain protein

nuclear protein

RUNX2 protein

human

transcription factor

transcription factor MSX2

transcription factor RUNX2

transcription factor Twist

TWIST1 protein

human

acrocephalosyndactyly

adult

article

breast tumor

DNA sequence

female

genetic screening

genetics

human

middle aged

mutation

polymerase chain reaction

tumor suppressor gene

Acrocephalosyndactylia

Breast Neoplasms

Core Binding Factor Alpha 1 Subunit

DNA-Binding Proteins

Ephrin-B1

Genes

BRCA1

Genes

BRCA2

Genetic Testing

Germ-Line Mutation

Homeodomain Proteins

Humans

Nuclear Proteins

Receptor

Fibroblast Growth Factor

Type 1

Receptor

Fibroblast Growth Factor

Type 2

Receptor

Fibroblast Growth Factor

Type 3

Receptor

Fibroblast Growth Factor

Type 4

Sequence Analysis

DNA

Transcription Factors

Twist Transcription Factor

Acrocephalosyndactylia

epidemiology

genetics

Adult

Breast Neoplasms

Core Binding Factor Alpha 1 Subunit

DNA-Binding Proteins

Ephrin-B1

Female

Genes

BRCA1

BRCA2

Genetic Testing

Germ-Line Mutation

Homeodomain Proteins

Humans

Middle Aged

Nuclear Proteins

Polymerase Chain Reaction

Receptor

Fibroblast Growth Factor

Type 1

Type 2

Type 3

Type 4

Sequence Analysis

DNA

Transcription Factors

Twist Transcription Factor

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