Genetic polymorphisms, methylation, and expression levels in the GSTP1 and MGMT genes in urothelial bladder tumors.

Background: Alteration in DNA repair and metabolism genes can affect the maintenance of DNA integrity or xenobiotics metabolism, potentially leading to DNA damage accumulation. The present study investigated the association between polymorphisms in Glutathione S-Transferase Pi 1 (GSTP1, rs1695) and O-6-Methylguanine-DNA Methyltransferase (MGMT, rs2308321) genes with urothelial bladder cancer (UBC) susceptibility and prognosis. Furthermore, the methylation patterns of the promoter region of these genes were analyzed in tumor and non-tumor bladder tissues, besides MGMT gene expression in tumor samples.

Plasma mutation profile of precursor lesions and colorectal cancer using the Oncomine Colon cfDNA Assay.

Background: Colorectal cancer (CRC) is the second leading cause of cancer death worldwide. Early detection of precursor lesions or early-stage cancer could hamper cancer development or improve survival rates. Liquid biopsy, which detects tumor biomarkers, such as mutations, in blood, is a promising avenue for cancer screening.

Enhancing Colorectal Cancer Screening with Droplet Digital PCR Analysis of Fusobacterium nucleatum in Fecal Immunochemical Test Samples.

Fecal immunochemical test (FIT) followed by colonoscopy in positive cases is commonly used for population-based colorectal cancer screening. However, specificity of FIT for colorectal cancer is not ideal and has poor performance for advanced adenoma detection. Fecal Fusobacterium nucleatum (Fn) detection has been proposed as a potential noninvasive biomarker for colorectal cancer and advanced adenoma detection.

Somatic mutational profiling and clinical impact of driver genes in Latin-Iberian medulloblastomas: Towards precision medicine.

Medulloblastoma (MB) is the most prevalent malignant brain tumor in children, known for its heterogeneity and treatment-associated toxicity, and there is a critical need for new therapeutic targets. We analyzed the somatic mutation profile of 15 driver genes in 69 Latin-Iberian molecularly characterized medulloblastomas using the Illumina TruSight Tumor 15 panel. We classified the variants based on their clinical impact and oncogenicity.

Combined SEPT9 and BMP3 methylation in plasma for colorectal cancer early detection and screening in a Brazilian population.

Background: Colorectal cancer (CRC) screening can help to reduce its incidence and mortality. Noninvasive strategies, such as plasma analysis of epigenetic alterations, can constitute important biomarkers of CRC detection.

Objective: This study aimed to evaluate the plasma methylation status of SEPT9 and BMP3 promoters as biomarkers for detection of CRC and its precursor lesions in a Brazilian population.

Somatic mutation detection and amplification in testicular germ cell tumors.

Background: Testicular Germ Cell Tumors (TGCT) are the most common cancer among young adult men. The TGCT histopathology is diverse, and the frequency of genomic alterations, along with their prognostic role, remains largely unexplored. Herein, we evaluate the mutation profile of a 15-driver gene panel and copy number variation of in a large series of TGCT from a single reference cancer center.

The potential of cell-free and exosomal microRNAs as biomarkers in liquid biopsy in patients with prostate cancer.

Purpose: Prostate cancer (PCa) is the 4th most diagnosed cancer and the 8th leading cause of cancer-related death worldwide. Currently, clinical risk stratification models including factors like PSA levels, Gleason score, and digital rectal examination are used for this purpose. There is a need for novel biomarkers that can distinguish between indolent and aggressive pathology and reduce the risk of overdiagnosis/overtreatment.

Somatic targeted mutation profiling of colorectal cancer precursor lesions.

Background: Most colorectal cancers (CRC) arise from precursor lesions. This study aimed to characterize the mutation profile of colorectal cancer precursor lesions in a Brazilian population.

Methods: In total, 90 formalin-fixed paraffin-embedded colorectal precursor lesions, including 67 adenomas, 7 sessile serrated lesions, and 16 hyperplastic polyps, were analyzed by next-generation sequencing using a panel of 50 oncogenes and tumor suppressor genes.

Polymorphic variants of the CASP3, CASP9, BCL-2 and NKX3-1 genes as candidate markers for prostate cancer susceptibility and poor prognosis.

Background: There is an ongoing search for molecular markers that are specific, sensitive, and able to predict the stage of prostate cancer (PCa), which is the second most prevalent type of cancer in men worldwide. This study examined whether different single nucleotide polymorphisms (SNPs) were reliable markers of susceptibility to and prognosis of PCa in a sample of Brazilian patients.

Methods And Results: DNA samples were extracted from peripheral blood cells of 283 PCa patients and matched with samples from healthy controls.

Accuracy and Clinical Relevance of Intra-Tumoral Detection in Formalin-Fixed Paraffin-Embedded (FFPE) Tissue by Droplet Digital PCR (ddPCR) in Colorectal Cancer.

The use of droplet digital PCR (ddPCR) to identify and quantify low-abundance targets is a significant advantage for accurately detecting potentially oncogenic bacteria. () is implicated in colorectal cancer (CRC) tumorigenesis and is becoming an important prognostic biomarker. We evaluated the detection accuracy and clinical relevance of Fn DNA by ddPCR in a molecularly characterized, formalin-fixed, paraffin-embedded (FFPE) CRC cohort previously analyzed by qPCR for levels.

A Unique Case Report of Infant-Type Hemispheric Glioma (Gliosarcoma Subtype) with TPR-NTRK1 Fusion Treated with Larotrectinib.

Herein, we present a rare case of a nine-month-old boy diagnosed with infant-type hemispheric glioma (gliosarcoma subtype) at the left frontal lobe. Following subtotal resection, the patient started chemotherapy with the BABY POG protocol. We describe the clinical diagnosis, histological characteristics, radiological features, molecular aspects, and management of this tumor.

Circulating tumor DNA (ctDNA) detection is associated with shorter progression-free survival in advanced melanoma patients.

BRAF, NRAS and TERT mutations occur in more than 2/3 of melanomas. Its detection in patient's blood, as circulating tumor DNA (ctDNA), represents a possibility for identification and monitoring of metastatic disease. We proposed to standardize a liquid biopsy platform to identify hotspot mutations in BRAF, NRAS and TERT in plasma samples from advanced melanoma patients and investigate whether it was associated to clinical outcome.

Feasibility of methylated ctDNA detection in plasma samples of oropharyngeal squamous cell carcinoma patients.

Background: Oropharyngeal squamous cell carcinomas (OpSCCs) are commonly associated with high rates of treatment failure.

Objectives: To evaluate methylation-based markers in plasma from OpSCC patients as emerging tools for accurate/noninvasive follow-up.

Methods: Pretreatment formalin-fixed paraffin-embedded (FFPE) biopsies (n = 52) and paired plasma (n = 15) were tested for the methylation of CCNA1, DAPK, CDH8, and TIMP3 by droplet digital PCR (ddPCR).

Germline Mutation in Resulting in Impaired Protein Stability is Associated with Familial Breast and Thyroid Cancer.

Multiple primary thyroid cancer (TC) and breast cancer (BC) are commonly diagnosed, and the lifetime risk for these cancers is increased in patients with a positive family history of both TC and BC. Although this phenotype is partially explained by or mutations, a significant number of patients are negative for these alterations. We judiciously recruited patients diagnosed with BC and/or TC having a family history of these tumors and assessed their whole-exome sequencing.

Expression of GNAS, TP53, and PTEN Improves the Patient Prognostication in Sonic Hedgehog (SHH) Medulloblastoma Subgroup.

Medulloblastoma (MB) is the most common malignant brain tumor in children. It is currently classified in four main molecular subgroups with different clinical outcomes: sonic hedgehog, wingless, group 3, and group 4 (MB, MB, MB, or MB). Presently, a 22-gene expression panel has been efficiently applied for molecular subgrouping using nCounter technology.

Loss of DNA methylation is related to increased expression of miR-21 and miR-146b in papillary thyroid carcinoma.

Background: DNA methylation in miRNA genes has been reported as a mechanism that may cause dysregulation of mature miRNAs and consequently impact the gene expression. This mechanism is largely unstudied in papillary thyroid carcinomas (PTC).

Methods: To identify differentially methylated miRNA-encoding genes, we performed global methylation analysis (Illumina 450 K), integrative analysis (TCGA database), data confirmation (pyrosequencing and RT-qPCR), and functional assays.

Integrated data analysis reveals potential drivers and pathways disrupted by DNA methylation in papillary thyroid carcinomas.

Background: Papillary thyroid carcinoma (PTC) is a common endocrine neoplasm with a recent increase in incidence in many countries. Although PTC has been explored by gene expression and DNA methylation studies, the regulatory mechanisms of the methylation on the gene expression was poorly clarified. In this study, DNA methylation profile (Illumina HumanMethylation 450K) of 41 PTC paired with non-neoplastic adjacent tissues (NT) was carried out to identify and contribute to the elucidation of the role of novel genic and intergenic regions beyond those described in the promoter and CpG islands (CGI).

Defining suitable reference genes for RT-qPCR analysis on human sertoli cells after 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) exposure.

Quantitative real-time RT-PCR (qPCR) has proven to be a valuable molecular technique to quantify gene expression. There are few studies in the literature that describe suitable reference genes to normalize gene expression data. Studies of transcriptionally disruptive toxins, like tetrachlorodibenzo-p-dioxin (TCDD), require careful consideration of reference genes.

Allelic variants of XRCC1 and XRCC3 repair genes and susceptibility of oral cancer in Brazilian patients.

Background: The capacity for DNA repair is essential in maintaining cellular functions and homeostasis; however, this capacity can be altered based on DNA sequence variations in DNA repair genes, which may contribute to the onset of cancer. Many single-nucleotide polymorphisms (SNPs) in repair genes have been found to be associated with oral cancer. The aim of this study was to investigate the relationship between the presence of allelic variants Arg194Trp (rs:1799782) and Arg399Gln (rs: 25487) of XRCC1 gene and Thr241Met (rs: 861539) of XRCC3 gene and susceptibility to oral cancer.

Mutagenicity and genotoxicity of isatin in mammalian cells in vivo.

Isatin (1H-indole-2,3-dione) is a synthetically versatile substrate used for the synthesis of heterocyclic compounds and as a raw material for drug synthesis. Isatin and its derivatives demonstrate anticonvulsant, antibacterial, antifungal, antiviral, and anticancer properties. We evaluated the genotoxic and mutagenic effects of acute (24h) and repeated (14d) exposure to isatin in vivo, using the comet assay and the micronucleus test.