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Integrative (genomic, transcriptomic and methylome) analyses of rectal cancer to unravel predictors of neoadjuvant treatment response

Grant number: 15/25803-4
Support type:Scholarships abroad - Research Internship - Doctorate (Direct)
Effective date (Start): April 08, 2016
Effective date (End): April 07, 2017
Field of knowledge:Health Sciences - Medicine - Pathological Anatomy and Clinical Pathology
Principal Investigator:Silvia Regina Rogatto
Grantee:Luisa Matos Do Canto Alvim
Supervisor abroad: Jan Baumbach
Home Institution: A C Camargo Cancer Center. Fundação Antonio Prudente (FAP). São Paulo , SP, Brazil
Local de pesquisa : University of Southern Denmark (SDU), Denmark  
Associated to the scholarship:14/06323-9 - Molecular markers identification of neoadjuvant treatment response in rectal adenocarcinoma patients, BP.DD

Abstract

Stage II-III rectal carcinoma (ReCa) patients undergo neoadjuvant chemoradiotherapy (nCRT) followed by surgery. Those who achieve pathological complete response (pCR) have better prognosis and could be spared of a highly morbid procedure if pCR was accurately identified precociously. However, the current molecular studies have shown inconclusive results. Our study aims to evaluate the genomic methylation profile of ReCa biopsies of patients that underwent nCRT and integrate the data with copy number and expression profiles from the same patients (data already obtained). The methylation profile will be obtained using a Platform from Illumina (450K), which provides methylation status of 96% of the CpG islands described. This project will be performed under the supervision of Dr. Rogatto, whose laboratory has an excellent infrastructure, well equipped to perform methylation experiments and analysis. Integration of omics data will be developed in collaboration with Dr. Jan Baumbach, who has an extensive experience in computational systems biomedicine research. The suggested project perfectly fits Baumbach's expertise in the combined analysis of multiple omics data types together with biochemical networks. It will prove particularly useful for unraveling new biomarkers allowing stratification of therapy, helping to recognize nCRT-sensitive patients and reducing the rate of postoperative morbidity. A comprehensive analysis of genetic and epigenetic alterations of rectal tumors from patients undergoing nCRT and its putative correlation to treatment response has the potential to identify molecular drivers useful for clinical practice. (AU)

Scientific publications
(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)
DO CANTO, LUISA MATOS; BARROS-FILHO, MATEUS CAMARGO; RAINHO, CLAUDIA APARECIDA; MARINHO, DIOGO; KUPPER, BRUNA ELISA CATIN; BEGNAMI, MARIA DIRLEI FERREIRA DE SOUZA; SCAPULATEMPO-NETO, CRISTOVAM; HAVELUND, BIRGITTE MAYLAND; LINDEBJERG, JAN; MARCHI, FABIO ALBUQUERQUE; BAUMBACH, JAN; AGUIAR, JR., SAMUEL; ROGATTO, SILVIA REGINA. Comprehensive Analysis of DNA Methylation and Prediction of Response to NeoadjuvantTherapy in Locally Advanced Rectal Cancer. CANCERS, v. 12, n. 11 NOV 2020. Web of Science Citations: 0.
DO CANTO, LUISA MATOS; CURY, SARAH SANTILONI; BARROS-FILHO, MATEUS CAMARGO; CATIN KUPPER, BRUNA ELISA; FERREIRA DE SOUZA BEGNAMI, MARIA DIRLEI; SCAPULATEMPO-NETO, CRISTOVAM; CARVALHO, ROBSON FRANCISCO; MARCHI, FABIO ALBUQUERQUE; OLSEN, DORTE AALUND; MADSEN, JONNA SKOV; HAVELUND, BIRGITTE MAYLAND; AGUIAR, JR., SAMUEL; ROGATTO, SILVIA REGINA. Locally advanced rectal cancer transcriptomic-based secretome analysis reveals novel biomarkers useful to identify patients according to neoadjuvant chemoradiotherapy response. SCIENTIFIC REPORTS, v. 9, JUN 18 2019. Web of Science Citations: 1.
DO CANTO, LUISA MATOS; LARSEN, SIMON J.; CATIN KUPPER, BRUNA E.; FERREIRA DE SOUZA BEGNAMI, MARIA DIRLEI; SCAPULATEMPO-NETO, CRISTOVAM; PETERSEN, ANNABETH HOGH; AAGAARD, MADS M.; BAUMBACH, JAN; AGUIAR JR, SAMUEL; ROGATTO, SILVIA R. Increased Levels of Genomic Instability and Mutations in Homologous Recombination Genes in Locally Advanced Rectal Carcinomas. FRONTIERS IN ONCOLOGY, v. 9, MAY 14 2019. Web of Science Citations: 0.

Please report errors in scientific publications list by writing to: cdi@fapesp.br.