| Grant number: | 13/13573-9 |
| Support Opportunities: | Scholarships abroad - Research Internship - Post-doctor |
| Start date: | December 01, 2013 |
| End date: | November 30, 2014 |
| Field of knowledge: | Health Sciences - Medicine - Medical Clinics |
| Principal Investigator: | Silvia Regina Caminada de Toledo |
| Grantee: | Carolina Salinas de Souza |
| Supervisor: | Adrienne Margaret Flanagan |
| Host Institution: | Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil |
| Institution abroad: | University College London (UCL), England |
| Associated to the scholarship: | 12/21193-9 - Determining the Clinical Impact of Genetic Alterations in Osteosarcoma, BP.PD |
Abstract Cancer is a genetic disease driven by somatically acquired point mutations. Osteosarcoma is the most common primary bone malignancy with a particularly high incidence in children and adolescents. Unlike many sarcomas, which are defined by specific chromosomal translocations, osteosarcoma is characterized by complex genomic alterations and high level heterogeneity. The mainstay of osteosarcoma treatment is preoperative chemotherapy followed by surgery. Nevertheless, 70% of patients still do not respond to chemotherapy, which is a strong predictor of poor 5-year survival. However, it is not possible to predict which tumours do not respond to therapy. Clinical researchers at the UCL Cancer Institute have collaborated with the Wellcome Trust Sanger Institute and performed either exome or whole genome sequencing of 80 osteosarcomas. The results, not yet published, represent the first stage in understanding the complexity of the osteosarcoma genome. However, it is now recognized that the genetic changes detected in a small area of a tumour does not provide a complete picture of a cancer's genetic heterogeneity which has developed over time. Therefore, the aim of this project is to determine the distribution of 100 recurrent mutations longitudinally (in time and space) in each of the 80 osteosarcoma cases using paraffin-embedded tumour tissues pre-chemotherapy. These genetic datasets will then be correlated with the histological grade and type, and clinical behaviour (recurrence and metastatic disease) and survival, thereby providing a landscape of the genetic evolution of the disease. The latest next-generation sequencing technology provided by Ion Torrent (Life Technologies) will be employed to screen for the known mutations. This will provide insight into the genetic complexity and heterogeneity in osteosarcoma and reveal the driver mutations that determine chemoresistance and tumour progression. (AU) | |
| News published in Agência FAPESP Newsletter about the scholarship: | |
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