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Combining genomic approaches to determine the genetics causes of rare cancers in children, adolescents and young adults

Grant number: 18/06269-5
Support type:Regular Research Grants
Duration: December 01, 2018 - November 30, 2020
Field of knowledge:Biological Sciences - Genetics
Principal Investigator:Giovana Tardin Torrezan
Grantee:Giovana Tardin Torrezan
Home Institution: A C Camargo Cancer Center. Fundação Antonio Prudente (FAP). São Paulo , SP, Brazil
Assoc. researchers: Diogo Cordeiro de Queiroz Soares ; Dirce Maria Carraro ; Maria Nirvana da Cruz Formiga ; MARIANA PETACCIA DE MACÊDO


Recent advances in genomics have enabled the recognition of several novel cancer predisposing genes. Although genetic screening is currently well established for more common hereditary cancers, there are a number of very rare tumors (annual incidence of less than 6 per 100,000 individuals) that are highly associated with cancer syndromes, but are often neglected due to its infrequency. The identification of the genetic causes of pediatric and adult rare tumors is important for the definition of better protocols for patient screening, clinical follow-up and familial management. In addition, knowledge of the molecular basis of the tumorigenesis in these tumors contributes to the understanding of different pathways and cellular processes involved in cell transformation and may become relevant for the definition of new therapies. Thus, the present study aims to determine the frequency of pathogenic germline mutations in known genes predisposing to cancer in children, adolescents and young adults (<40 years) with rare tumors. To accomplish that, we will evaluate the coding sequences of 106 moderate to high penetrance genes associated to hereditary cancers using next generation sequence. Furthermore, in a subset of these patients without any probably pathogenic germline variants, we will use combined genomic approaches (whole exome sequencing of germline and tumor cells and tumor transcriptome analysis) to determine new genetic causes and underlying biological pathways of these cancers. With this work, we hope to contribute to the definition of more effective and adequate genetic screening strategies for the Brazilian population with rare tumors and for the translation of complex genetics knowledge into better clinical care. (AU)