Publications by authors named "Rodrigo Duarte Drummond"

3 Publications

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Mutational Signatures Driven by Epigenetic Determinants Enable the Stratification of Patients with Gastric Cancer for Therapeutic Intervention.

Cancers (Basel) 2021 Jan 27;13(3). Epub 2021 Jan 27.

Laboratory of Bioinformatics and Computational Biology, A.C. Camargo Cancer Center, São Paulo 01508-010, Brazil.

DNA mismatch repair deficiency (dMMR) is associated with the microsatellite instability (MSI) phenotype and leads to increased mutation load, which in turn may impact anti-tumor immune responses and treatment effectiveness. Various mutational signatures directly linked to dMMR have been described for primary cancers. To investigate which mutational signatures are associated with prognosis in gastric cancer, we performed a extraction of mutational signatures in a cohort of 787 patients. We detected three dMMR-related signatures, one of which clearly discriminates tumors with gene silencing caused by promoter hypermethylation (area under the curve = 98%). We then demonstrated that samples with the highest exposure of this signature share features related to better prognosis, encompassing clinical and molecular aspects and altered immune infiltrate composition. Overall, the assessment of the prognostic value and of the impact of modifications in MMR-related genes on shaping specific dMMR mutational signatures provides evidence that classification based on mutational signature exposure enables prognosis stratification.
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http://dx.doi.org/10.3390/cancers13030490DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7866019PMC
January 2021

Influence of BRCA1 Germline Mutations in the Somatic Mutational Burden of Triple-Negative Breast Cancer.

Transl Oncol 2019 Nov 13;12(11):1453-1460. Epub 2019 Aug 13.

CIPE, International Research Center, A.C. Camargo Cancer Center, São Paulo, SP, Brazil; National Institute of Science and Technology in Oncogenomics and Therapeutic Innovation, São Paulo, SP, Brazil. Electronic address:

The majority of the hereditary triple-negative breast cancers (TNBCs) are associated with BRCA1 germline mutations. Nevertheless, the understanding of the role of BRCA1 deficiency in the TNBC tumorigenesis is poor. In this sense, we performed whole-exome sequencing of triplet samples (leucocyte, tumor, and normal-adjacent breast tissue) for 10 cases of early-onset TNBC, including 5 hereditary (with BRCA1 germline pathogenic mutation) and 5 sporadic (with no BRCA1 or BRCA2 germline pathogenic mutations), for assessing the somatic mutation repertoire. Protein-affecting somatic mutations were identified for both mammary tissues, and Ingenuity Pathway Analysis was used to investigate gene interactions. BRCA1 and RAD51C somatic promoter methylation in tumor samples was also investigated by bisulfite sequencing. Sporadic tumors had higher proportion of driver mutations (≥25% allele frequency) than BRCA1 hereditary tumors, whereas no difference was detected in the normal breast samples. Distinct gene networks were obtained from the driver genes in each group. The Cancer Genome Atlas data analysis of TNBC classified as hereditary and sporadic reinforced our findings. The data presented here indicate that in the absence of BRCA1 germline mutations, a higher number of driver mutations are required for tumor development and that different defective processes are operating in the tumorigenesis of hereditary and sporadic TNBC in young women.
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http://dx.doi.org/10.1016/j.tranon.2019.07.016DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6706625PMC
November 2019

Transcriptionally active transposable elements in recent hybrid sugarcane.

Plant J 2005 Dec;44(5):707-17

Departamento de Botânica, IB-USP, São Paulo, Brazil.

Transposable elements (TEs) are considered to be important components of the maintenance and diversification of genomes. The recent increase in genome sequence data has created an opportunity to evaluate the impact of these active mobile elements on the evolution of plant genomes. Analysis of the sugarcane transcriptome identified 267 clones with significant similarity to previously described plant TEs. After full cDNA sequencing, 68 sugarcane TE clones were assigned to 11 families according to their best sequence alignment against a fully characterized element. Expression was further investigated through a combined study utilizing electronic Northerns, macroarray, transient and stable sugarcane transformation. Newly synthesized cDNA probes from flower, leaf roll, apical meristem and callus tissues confirm previous results. Callus was identified as the tissue with the highest number of TEs being expressed, revealing that tissue culture drastically induced the expression of different elements. No tissue-specific family was identified. Different representatives within a TE family displayed differential expression patterns, showing that each family presented expression in almost every tissue. Transformation experiments demonstrated that most Hopscotch clone-derived U3 regions are, indeed, active promoters, although under a strong transcriptional regulation. This is a large-scale study about the expression pattern of TEs and indicates that mobile genetic elements are transcriptionally active in the highly polyploid and complex sugarcane genome.
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http://dx.doi.org/10.1111/j.1365-313X.2005.02579.xDOI Listing
December 2005