Mutation analysis of the AATF gene in breast cancer families
Maria Haanpää1, Mervi Reiman, Jenni Nikkilä
1Laboratory of Cancer Genetics, Oulu University Hospital, P,O, Box 22, FIN-90221 Oulu, Finland. maappi@mail.student.oulu.fi
Background:
About 5-10% of breast cancer is due to inherited disease predisposition. Many previously identified susceptibility factors are involved in the maintenance of genomic integrity. AATF plays an important role in the regulation of gene transcription and cell proliferation. It induces apoptosis by associating with p53. The checkpoint kinases ATM/ATR and CHEK2 interact with and phosphorylate AATF, enhancing its accumulation and stability. Based on its biological function, and direct interaction with several known breast cancer risk factors, AATF is a good candidate gene for being involved in heritable cancer susceptibility.
Methods:
Here we have screened the entire coding region of AATF in affected index cases from 121 Finnish cancer families for germline defects, using conformation sensitive gel electrophoresis and direct sequencing.
Results:
Altogether seven different sequence changes were observed, one missense variant and six intronic ones. Based on the in silico analyses of these sequence alterations, as well as their occurrence in cases and controls, none of them, however, were predicted to be pathogenic.
Conclusions:
To our knowledge, this is the first study reporting the mutation screening of the AATF gene in familial breast cancer cases. No evidence for the association with breast cancer was observed.
Insights
This study investigated the AATF gene in Finnish families with a history of breast cancer. No disease-causing mutations were found, suggesting AATF is not a significant factor in inherited breast cancer risk.
Area of Science:
- Genetics
- Oncology
- Molecular Biology
Background:
- Inherited predisposition accounts for 5-10% of breast cancer cases.
- Susceptibility factors often maintain genomic integrity.
- The AATF gene regulates transcription, cell proliferation, and apoptosis, interacting with known breast cancer risk factors like p53 and ATM/ATR/CHEK2.
Purpose of the Study:
- To screen the AATF gene for germline mutations in Finnish familial breast cancer cases.
- To evaluate the potential role of AATF in heritable breast cancer susceptibility.
Main Methods:
- Screened the entire coding region of the AATF gene.
- Utilized conformation sensitive gel electrophoresis and direct sequencing.
- Analyzed 121 affected index cases from Finnish cancer families.
Main Results:
- Identified seven sequence variations: one missense and six intronic.
- In silico analyses and case-control comparisons indicated no pathogenic variants.
- No significant association between AATF mutations and familial breast cancer was observed.
Conclusions:
- This is the first study to screen the AATF gene for mutations in familial breast cancer.
- The findings do not support AATF as a major susceptibility gene for breast cancer in the studied Finnish population.
