Background: In the phase 3 GRID trial, regorafenib improved progression-free survival (PFS) independent of KIT mutations in exons 9 and 11. In this retrospective, exploratory analysis of the GRID trial, we investigated whether a more comprehensive KIT mutation analysis could identify mutations that impact treatment outcome with regorafenib and a regorafenib-induced mutation pattern.
Methods: Archived tumor samples, collected at any time prior to enrollment in GRID, were analyzed by Sanger sequencing (n = 102) and next-generation sequencing (FoundationONE; n = 47).
Mem Inst Oswaldo Cruz
March 2017
Background: Two novel viruses named circo-like virus-Brazil (CLV-BR) hs1 and hs2 were previously discovered in a Brazilian human fecal sample through metagenomics. CLV-BR hs1 and hs2 possess a small circular DNA genome encoding a replication initiator protein (Rep), and the two genomes exhibit 92% nucleotide identity with each other. Phylogenetic analysis based on the Rep protein showed that CLV-BRs do not cluster with circoviruses, nanoviruses, geminiviruses or cycloviruses.
View Article and Find Full Text PDFObjectives: Making liquid biopsy testing widely available requires a concept to ship whole blood at ambient temperatures while retaining the integrity of the cell-free DNA (cfDNA) population and stability of blood cells to prevent dilution of circulating tumor DNA (ctDNA) with wild-type genomic DNA. The cell- and DNA-stabilizing properties of Streck Cell-Free DNA BCT blood collection tubes (cfDNA BCTs) were evaluated to determine if they can be utilized in combination with highly sensitive mutation detection technologies.
Methods: Venous blood from healthy donors or patients with advanced colorectal cancer (CRC) was collected in cfDNA BCTs and standard K2EDTA tubes.
We have designed a highly sensitive assay based on the Safe-SeqS technology to detect de novo mutations in the KIT gene and tested its performance. This assay was applied to plasma samples of GIST patients before and after treatment with regorafenib (GRID III trial) and mutations at known and novel sites of potential secondary resistance were identified.
View Article and Find Full Text PDFFibropapillomatosis (FP), a neoplastic disease characterized by the formation of multiple tumors affecting different species of sea turtles and, most often, the green turtle (Chelonia mydas), is considered one of the major threats to the survival of this species. Recent studies indicate that Chelonid herpesvirus (ChHV5) is the etiological agent of this disease, though its association with anthropogenically altered environments and the immune status of these animals also appears to contribute to disease expression and tumor formation. In this study, tumor biopsy and secretions from green turtles captured off the coast of São Paulo State, Brazil, were used in histological and molecular analyses to detect and characterize circulating ChHV5.
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