Center for Medical Genetics Center for Medical Genetics

Hereditary Breast Cancer

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The most and best studied genes in the world are probably BRCA1 and BRCA2. Since their identification in 1994 en 1995, large improvements in the technologies allowed the identification of deleterious mutations in millions of breast cancer patients. Our research team strongly contributed to insights in the mutation spectrum and frequency in Belgian patients.

Through translational research our team aims to contribute to the improvement of the prevention, diagnosis and treatment of hereditary breast cancer by extensive molecular characterization of germline and somatic mutations. Besides the study of mutations/variants in the coding regions, research projects are ongoing to determine the role of variants in non-coding and regulatory regions. Furthermore, we have a major interest in the development of in vitro and in vivo functional tests to determine the clinical significance of genetic variants.

Besides hereditary breast cancer, our team also performs case-related research in the context of other familial cancer syndromes (hereditary colon cancer, pancreatic cancer, etc.)

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Mutations in BRCA1 and BRCA2, are associated with highly increased risks for breast cancer. If a germline mutation is identified in the proband, predictive testing can be offered to relatives who will benefit from options available for early cancer detection and prevention. Germline mutations in BRCA1/2 account for less than 30% of breast cancer in families that contain up to five cases of breast cancer. Several explanations for this 'missing heritability' have been proposed, including the existence of many but individually very rare variants. With the advent of next generation sequencing technologies it becomes possible to screen a large number of additional breast cancer genes in a large number of patients at a relatively low cost. To identify more of the ‘missing heritability’ of breast cancers we are evaluating the mutation spectrum in the coding and non-coding regions of additional breast cancer genes in our patient population applying novel sequencing technologies.

The generation of large sequencing data sets, leads to the identification of a Variant of Unknown Significance (VUS) in several index patients. These individually rare VUS potentially have a negative impact on the particular patient as they create greater uncertainty and need further investigations for adequate interpretation. The currently known breast cancer genes are all involved in DNA repair. We are exploring the application of irradiation-based tests to evaluate the functional effects of VUS in these genes. We are developing in vitro tests (in lymphocytes of patients) and in vivo tests (in zebrafish).

For the design of efficient therapies the identification of somatic alterations in genes and pathways that play key roles in tumor initiation and progression is important. We aim to study mechanisms of tumorigenesis in inherited breast cancer, which may ultimately result in the development of improved therapies.

Last updated: 08 December 2015 - 15:45
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