The overall aim for the research in this team is to achieve improved patient handling in clinical oncology with specific focus on lymphoma and breast cancer. Our projects concern the use of circulating tumor DNA as a biomarker for prediction and treatment in breast cancer; and characterization of mutations in the Swedish germ-line TP53 cohort.
More specifically the research focus in the different projects are:
Circulating Tumor DNA as a Biomarker for Breast Cancer.
There is growing confidence that the next generation of screening tests will be based on molecular biomarkers present in bodily fluids. It is based on evidence that tumors release significant amounts of free circulating DNA (ctDNA) into the blood stream due to cellular necrosis and apoptosis in the tumor. ctDNA bears the same genetic alterations as the tumor tissue, and genotyping of ctDNA in the serum provides an accurate picture of the genetic profile of the tumor. Since ctDNA is isolated from serum after a simple blood collection, one of the less invasive and most robust sampling procedures, it can be performed multiple times to monitor tumor progression during follow-up of breast cancer patients. Moreover, the same approach can be used to monitor tumor development in healthy high-risk mutation carriers.
The following questions are approached in this project:
- How ctDNA can be used as a biomarker for screening and for early detection of breast cancer in high-risk individuals with mutations in BRCA1, BRCA2 and TP53.
- How ctDNA can be used for follow up of breast cancer patients and detection of early relapse.
- How can genetic alterations found in ctDNA be used as surrogate biomarkers to improve investigation and management of breast cancer patients.
- How can ctDNA genotyping be used to complement and/or substitute to tumor genotyping for treatment decision.
The Swedish Constitutional TP53 Cohort
The Li-Fraumeni Syndrome (LFS) is associated with constitutional mutations in the TP53-gene, a rare disorder with a high risk of mainly osteosarcoma, soft tissue sarcomas, breast-, brain- and/or adrenocortical tumors, particularly in children and young adults. Germ-line mutations in TP53 have also been described as a cause of hereditary breast cancer. It is therefore important to characterize the TP53 families and to outline the mutation spectrum in families with LFS or LFS-like history versus those with only hereditary breast cancer.
Recent reports have indicated that mutation carriers may benefit from a surveillance program. In Sweden, a national clinical TP53 study group was formed in 2013. The overall objective is to improve the survival of these patients by establishing a nation-wide registry for families with TP53 mutations and to develop and implement a clinical surveillance program for molecularly defined LFS-families.
The overall aim of this project is to characterize and outline the impact of the germ-line TP53 mutations identified in families with a LFS tumor spectra compared to families with hereditary breast cancer in order to increase the knowledge of the disease panorama in these families. Furthermore, we want to develop and evaluate a surveillance program for families with a constitutional TP53 mutation in Sweden in order to increase the survival of these patients.