Exploring cross-tissue DNA methylation patterns: blood-brain CpGs as potential neurodegenerative disease biomarkers.

The difficulty of obtaining samples from certain human tissues has led to efforts to find accessible sources to analyze molecular markers derived from DNA. In this study, we look for DNA methylation patterns in blood samples and its association with the brain methylation pattern in neurodegenerative disorders. Using data from methylation databases, we selected 18,293 CpGs presenting correlated methylation levels between blood and brain (bb-CpGs) and compare their methylation level between blood samples from patients with neurodegenerative diseases (Alzheimer's disease, Parkinson's disease, Multiple Sclerosis, and X Fragile Syndrome) and healthy controls.

BRCA1, BRCA2, and TP53 germline and somatic variants and clinicopathological characteristics of Brazilian patients with epithelial ovarian cancer.

Background: Approximately 3/4 of ovarian cancers are diagnosed in advanced stages, with the high-grade epithelial ovarian carcinoma (EOC) accounting for 90% of the cases. EOC present high genomic instability and somatic loss-of-function variants in genes associated with homologous recombination mutational repair pathway (HR), such as BRCA1 and BRCA2, and in TP53. The identification of germline variants in HR genes in EOC is relevant for treatment of platinum resistant tumors and relapsed tumors with therapies based in synthetic lethality such as PARP inhibitors.

Naso-oropharyngeal microbiome from breast cancer patients diagnosed with COVID-19.

Due to immunosuppressive cancer therapies, cancer patients diagnosed with COVID-19 have a higher chance of developing severe symptoms and present a higher mortality rate in comparison to the general population. Here we show a comparative analysis of the microbiome from naso-oropharyngeal samples of breast cancer patients with respect to SARS-CoV-2 status and identified bacteria associated with symptom severity. Total DNA of naso-oropharyngeal swabs from 74 women with or without breast cancer, positive or negative for SARS-CoV-2 were PCR-amplified for 16S-rDNA V3 and V4 regions and submitted to massive parallel sequencing.

High APOBEC3B mRNA Expression Is Associated with Human Papillomavirus Type 18 Infection in Cervical Cancer.

The APOBEC3 (A3) proteins are cytidine deaminases that exhibit the ability to insert mutations in DNA and/or RNA sequences. APOBEC3B (A3B) has been evidenced as a DNA mutagen with consistent high expression in several cancer types. Data concerning the A3B influence on HPV infection and cervical cancer are limited and controversial.

Familial history and prevalence of BRCA1, BRCA2 and TP53 pathogenic variants in HBOC Brazilian patients from a public healthcare service.

Several studies have demonstrated the cost-effectiveness of genetic testing for surveillance and treatment of carriers of germline pathogenic variants associated with hereditary breast/ovarian cancer syndrome (HBOC). In Brazil, seventy percent of the population is assisted by the public Unified Health System (SUS), where genetic testing is still unavailable. And few studies were performed regarding the prevalence of HBOC pathogenic variants in this context.

Molecular alterations in retinoblastoma beyond RB1.

Retinoblastoma is the most common malignant ocular tumor in children. Although RB1 alterations are most frequently involved in the etiology of retinoblastoma, candidate driver events and somatic alterations leading to cell transformation, tumor onset and progression remain poorly understood. In this study, we identified novel genomic alterations in tumors with a panel of 160 genes.

Expression of Retroelements in Cervical Cancer and Their Interplay with HPV Infection and Host Gene Expression.

Retroelements are expressed in diverse types of cancer and are related to tumorigenesis and to cancer progression. We characterized the expression of retroelements in cervical cancer and explored their interplay with HPV infection and their association with expression of neighboring genes. Forty biopsies of invasive cervical carcinoma (squamous cell carcinomas and adenocarcinomas) with genotyped HPV were selected and analyzed for human endogenous retrovirus (HERV) and long interspersed nuclear element 1 (L1) expression through RNA-seq data.

Transcriptome of the Southern Muriqui (Primates:Platyrrhini), a Critically Endangered New World Monkey: Evidence of Adaptive Evolution.

The southern muriqui () is the largest neotropical primate. This species is endemic to Brazil and is currently critically endangered due to its habitat destruction. The genetic basis underlying adaptive traits of New World monkeys has been a subject of interest to several investigators, with significant concern about genes related to the immune system.

Haplotypic characterization of BRCA1 c.5266dupC, the prevailing mutation in Brazilian hereditary breast/ovarian cancer.

Specific pathogenic mutations associated with breast cancer development can vary between ethnical groups. One example is BRCA1 c.5266dupC that was first described as a founder mutation in the Ashkenazi Jewish population, but was later also found in other populations.

Overweight and obesity do not determine worst prognosis in endometrioid endometrial carcinoma.

Purpose: The aim of this study was to investigate the impact of body mass index (BMI) on disease-free survival (DFS) and overall survival (OS) in women diagnosed with EEC and treated at the Brazilian National Cancer Institute.

Methods: The study comprised 849 women diagnosed with EEC who underwent surgical treatment between January, 2000 and December, 2011. The demographic and clinical characteristics of these patients were collected from medical records and their nutritional status was based on the BMI criteria.

Factors associated with cervical intraepithelial neoplasia (CIN2/CIN3), early stage and advanced stage of cervical cancer diagnosis in the Brazilian Amazonian region.

To understand the impact of demographic, behavioral and contextual factors on cervical cancer, we examined the profile of women classified according to cervical cancer staging [precursor lesions cervical intraephitelial neoplasia (CIN2/CIN3), early- and advanced-stage cancer]. Patients were identified in the main oncological reference hospital in Pará State, Brazil, from 2013 through 2015. Adjusted prevalence ratios and their respective 95% confidence intervals were estimated using Poisson regression with robust variance.

HPV73 a nonvaccine type causes cervical cancer.

HPV73 is classified as possibly oncogenic. It is neither routinely evaluated in HPV screening, nor covered by any of the prophylactic vaccines. We sought to investigate the carcinogenic characteristics of HPV73.

Methylation of p16 ink4a promoter is independent of human papillomavirus DNA physical state: a comparison between cervical pre-neoplastic and neoplastic samples.

BACKGROUND Epigenetic modifications in host cells, like p16 ink4a methylation, have been considered as putative complementary mechanisms for cancer development. Because only a small proportion of infected women develop cervical cancer, other factors might be involved in carcinogenesis, either independently or in association with high-risk human papillomavirus (HR-HPV) infections, including epigenetic factors. OBJECTIVES We hypothesised that p16 ink4a methylation might have a role in cancer development driven by HPV16, mainly in the presence of intact E1/E2 genes.

Screening and characterization of BRCA2 c.156_157insAlu in Brazil: Results from 1380 individuals from the South and Southeast.

Portuguese immigration to Brazil occurred in several waves and greatly contributed to the genetic composition of current Brazilian population. In this study, we evaluated the frequency of a Portuguese founder Alu insertion in BRCA2 exon 3 (c.156_157insAlu) among individuals fulfilling Hereditary Breast and Ovarian Cancer (HBOC) syndrome criteria in 1,380 unrelated families originated from three distinct Brazilian States.

Characterization of HPV integration, viral gene expression and E6E7 alternative transcripts by RNA-Seq: A descriptive study in invasive cervical cancer.

Scarce data are available on the expression of papillomavirus genome and the frequency of alternatively spliced E6E7 mRNAs in invasive cervical cancer. We carried out a comprehensive characterization of HPV expression by RNA-Seq analysis in 22 invasive cervical cancer with HPV16 or HPV18, characterizing the presence of integrated/episomal viral DNA, the integration sites in human genome and the proportion of alternative splicing products of E6 and E7 genes. The expression patterns suggested the presence of episomal and/or integrated viral DNA, with integration detected in most tumors, frequently occurring within human genes in HPV18+ and in intergenic regions in HPV16+ tumors.

Mutations, Differential Gene Expression, and Chimeric Transcripts in Esophageal Squamous Cell Carcinoma Show High Heterogeneity.

Esophageal squamous cell carcinoma (ESCC) is a frequent and lethal neoplasia. As recent advances in targeted therapy have not improved ESCC prognosis, characterization of molecular alterations associated to this tumor is of foremost relevance. In this study, we analyze, for the first time, the complete genomic profile of ESCC by RNA-seq.

The germline mutational landscape of BRCA1 and BRCA2 in Brazil.

The detection of germline mutations in BRCA1 and BRCA2 is essential to the formulation of clinical management strategies, and in Brazil, there is limited access to these services, mainly due to the costs/availability of genetic testing. Aiming at the identification of recurrent mutations that could be included in a low-cost mutation panel, used as a first screening approach, we compiled the testing reports of 649 probands with pathogenic/likely pathogenic variants referred to 28 public and private health care centers distributed across 11 Brazilian States. Overall, 126 and 103 distinct mutations were identified in BRCA1 and BRCA2, respectively.

HPV DNA methylation at the early promoter and E1/E2 integrity: A comparison between HPV16, HPV18 and HPV45 in cervical cancer.

Objectives: To compare and describe type-specific characteristics of HPV16, HPV18 and HPV45 in cervical cancer with respect to 3'LCR methylation and disruption of E1/E2.

Methods: The methylation level of 137 cervical cancer samples (70 with HPV16, 37 with HPV18, and 30 with HPV45) of Brazilian patients was analyzed by pyrosequencing. PCR amplifications were performed to characterize E1 and E2 disruption as an episomal surrogate.

Germline MLH1, MSH2 and MSH6 variants in Brazilian patients with colorectal cancer and clinical features suggestive of Lynch Syndrome.

Lynch syndrome (LS) is the most common hereditary colorectal cancer syndrome, caused by germline mutations in one of the major genes involved in mismatch repair (MMR): MLH1, MSH2, MSH6 and more rarely, PMS2. Recently, germline deletions in EPCAM have been also associated to the syndrome. Most of the pathogenic MMR mutations found in LS families occur in MLH1 or MSH2.