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

• Grant number: 18/06269-5
• Support Opportunities: Regular Research Grants
• Start date: December 01, 2018
• End date: November 30, 2021
• Field of knowledge: Biological Sciences - Genetics - Human and Medical Genetics
• Principal Investigator: Giovana Tardin Torrezan
• Grantee: Giovana Tardin Torrezan
• Host Institution: A C Camargo Cancer Center. Fundação Antonio Prudente (FAP). São Paulo , SP, Brazil
• Associated researchers: Diogo Cordeiro de Queiroz Soares ; Dirce Maria Carraro ; Maria Nirvana da Cruz Formiga ; Mariana Petaccia de Macêdo
• Associated research grant(s): 20/00870-9 - Genomic drivers of pediatric and early-onset solid tumors, AP.R SPRINT

Abstract

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)

Scientific publications

(5)

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

DE CARVALHO, NATHALIA DE ANGELIS; NIITSUMA, BIANCA NAOMI; KOZAK, VANESSA NASCIMENTO; COSTA, FELIPE D'ALMEIDA; DE MACEDO, MARIANA PETACCIA; CATIN KUPPER, BRUNA ELISA; GOBO SILVA, MARIA LETICIA; FORMIGA, MARIA NIRVANA; VOLC, SAHLUA MIGUEL; AGUIAR JUNIOR, JR., SAMUEL; et al. Clinical and Molecular Assessment of Patients with Lynch Syndrome and Sarcomas Underpinning the Association withMSH2Germline Pathogenic Variants. CANCERS, v. 12, n. 7, JUL 2020. (18/06269-5, 14/50943-1)

SIMOES, MARIA FERNANDA EVANGELISTA; DA COSTA, ALEXANDRE ANDRE BALIEIRO ANASTACIO; SILVA, TULLIO NOVAES; FERNANDES, LIZIEUX; BOVOLIM, GRAZIELE; TORREZAN, GIOVANA TARDIN; CARRARO, DIRCE MARIA; BAIOCCHI, GLAUCO; MENEZES, ADEMIR NARCIZO OLIVEIRA; SANTANA DOS SANTOS, ELIZABETH; et al. Case Report of Small Cell Carcinoma of the Ovary, Hypercalcemic Type (Ovarian Rhabdoid Tumor) with SMARCB1 Mutation: A Literature Review of a Rare and Aggressive Condition. CURRENT ONCOLOGY, v. 29, n. 2, p. 12-pg., 2022-02-01. (14/50943-1, 18/06269-5)

MELLO, CELSO ABDON; BATISTA CAMPOS, FERNANDO AUGUSTO; SANTOS, TIAGO GOSS; GOBO SILVA, MARIA LETICIA; TORREZAN, GIOVANA TARDIN; COSTA, FELIPE D'ALMEIDA; FORMIGA, MARIA NIRVANA; NICOLAU, ULISSES; NASCIMENTO, ANTONIO GERALDO; SILVA, CASSIA; et al. Desmoplastic Small Round Cell Tumor: A Review of Main Molecular Abnormalities and Emerging Therapy. CANCERS, v. 13, n. 3, FEB 2021. (14/50943-1, 18/06269-5, 18/25541-8)

RIECHELMANN, RACHEL P.; SOARES, DIOGO C.; DIAS, CARLA; CARRARO, DIRCE M.; TORREZAN, GIOVANA. Li-Fraumeni-associated pancreatic neuroendocrine tumour and XAF1 p.Glu134Ter risk modifier variant. ECANCERMEDICALSCIENCE, v. 16, p. 5-pg., 2022-12-08. (14/50943-1, 18/06269-5)

RIECHELMANN, RACHEL P.; DONADIO, MAURO D.; BARROS, MILTON; SANTIAGO, KARINA M.; CARVALHO, NATHALIA A.; LOPEZ, LAURA; CARRARO, DIRCE M.; TORREZAN, GIOVANA T.. High rate of pathogenic germline variants in young patients with neuroendocrine tumors. European Journal of Human Genetics, v. 30, n. SUPPL 1, p. 2-pg., 2022-04-01. (18/06269-5)