The Mutographs biorepository: A unique genomic resource to study cancer around the world.

Large-scale biorepositories and databases are essential to generate equitable, effective, and sustainable advances in cancer prevention, early detection, cancer therapy, cancer care, and surveillance. The Mutographs project has created a large genomic dataset and biorepository of over 7,800 cancer cases from 30 countries across five continents with extensive demographic, lifestyle, environmental, and clinical information. Whole-genome sequencing is being finalized for over 4,000 cases, with the primary goal of understanding the causes of cancer at eight anatomic sites.

Folic Acid and Vitamin B12 Prevent Deleterious Effects of Rotenone on Object Novelty Recognition Memory and Expression in an Animal Model of Parkinson's Disease.

Parkinson's disease (PD) is characterized by a range of motor signs, but cognitive dysfunction is also observed. Supplementation with folic acid and vitamin B12 is expected to prevent cognitive impairment. To test this in PD, we promoted a lesion within the substantia nigra of rats using the neurotoxin rotenone.

Body Hypomethylation Is Frequent in Tumors from the Digestive and Respiratory Tracts and Is Associated with Risk-Factor Exposure.

Squamous cell carcinoma is the main histological tumor type in the upper aerodigestive tract (UADT), including the esophagus (ESCC) and the head and neck sites, as well as the oral cavity (OCSCC), larynx (LSCC) and oropharynx (OPSCC). These tumors are induced by alcohol and tobacco exposure, with the exception of a subgroup of OPSCC linked to human papillomavirus (HPV) infection. Few genes are frequently mutated in UADT tumors, pointing to other molecular mechanisms being involved during carcinogenesis.

Molecular mechanisms associated with chemoresistance in esophageal cancer.

Esophageal cancer (EC) is one of the most incident and lethal tumors worldwide. Although surgical resection is an important approach in EC treatment, late diagnosis, metastasis and recurrence after surgery have led to the management of adjuvant and neoadjuvant therapies over the past few decades. In this scenario, 5-fluorouracil (5-FU) and cisplatin (CISP), and more recently paclitaxel (PTX) and carboplatin (CBP), have been traditionally used in EC treatment.

Head and Neck Cancers Are Not Alike When Tarred with the Same Brush: An Epigenetic Perspective from the Cancerization Field to Prognosis.

Head and neck squamous cell carcinomas (HNSCC) are among the ten most frequent types of cancer worldwide and, despite all efforts, are still diagnosed at late stages and show poor overall survival. Furthermore, HNSCC patients often experience relapses and the development of second primary tumors, as a consequence of the field cancerization process. Therefore, a better comprehension of the molecular mechanisms involved in HNSCC development and progression may enable diagnosis anticipation and provide valuable tools for prediction of prognosis and response to therapy.

HPV Infection Leaves a DNA Methylation Signature in Oropharyngeal Cancer Affecting Both Coding Genes and Transposable Elements.

HPV oncoproteins can modulate DNMT1 expression and activity, and previous studies have reported both gene-specific and global DNA methylation alterations according to HPV status in head and neck cancer. However, validation of these findings and a more detailed analysis of the transposable elements (TEs) are still missing. Here we performed pyrosequencing to evaluate a 5-CpG methylation signature and Line1 methylation in an oropharyngeal squamous cell carcinoma (OPSCC) cohort.

Upper Aerodigestive Tract Squamous Cell Carcinomas Show Distinct Overall DNA Methylation Profiles and Different Molecular Mechanisms behind WNT Signaling Disruption.

Upper aerodigestive tract (UADT) tumors present different biological behavior and prognosis, suggesting specific molecular mechanisms underlying their development. However, they are rarely considered as single entities (particularly head and neck subsites) and share the most common genetic alterations. Therefore, there is a need for a better understanding of the global DNA methylation differences among UADT tumors.

DNA Methylation Markers from Negative Surgical Margins Can Predict Recurrence of Oral Squamous Cell Carcinoma.

The identification of molecular markers in negative surgical margins of oral squamous cell carcinoma (OSCC) might help in identifying residual molecular aberrations, and potentially improve the prediction of prognosis. We performed an Infinium MethylationEPIC BeadChip array on 32 negative surgical margins stratified based on the status of tumor recurrence in order to identify recurrence-specific aberrant DNA methylation (DNAme) markers. We identified 2512 recurrence-associated Differentially Methylated Positions (DMPs) and 392 Differentially Methylated Regions (DMRs) which were enriched in cell signaling and cancer-related pathways.

HMGA1 induces EZH2 overexpression in human B-cell lymphomas.

EZH2 is an enzymatic subunit of PRC2, an epigenetic regulator that triggers the methylation of the histone H3 lysine 27 silencing the transcription of several genes. EZH2 has a critical role in cancer progression, since its overexpression has been associated with increased cancer cell invasiveness, drug resistance and poor patient survival. However, the mechanisms accounting for EZH2 overexpression in cancer remain still unclear.

Potential Therapeutic Significance of Laminin in Head and Neck Squamous Carcinomas.

Head and neck squamous cell carcinomas (HNSCC) are among the most common and lethal tumors worldwide, occurring mostly in oral cavity, pharynx, and larynx tissues. The squamous epithelia homeostasis is supported by the extracellular matrix (ECM), and alterations in this compartment are crucial for cancer development and progression. Laminin is a fundamental component of ECM, where it represents one of the main components of basement membrane (BM), and data supporting its contribution to HNSCC genesis and progression has been vastly explored in oral cavity squamous cell carcinoma.

GLIPR1 and SPARC expression profile reveals a signature associated with prostate Cancer Brain metastasis.

Despite advances in treatment of lethal prostate cancer, the incidence of prostate cancer brain metastases is increasing. In this sense, we analyzed the molecular profile, as well as the functional consequences involved in the reciprocal interactions between prostate tumor cells and human astrocytes. We observed that the DU145 cells, but not the LNCaP cells or the RWPE-1 cells, exhibited more pronounced, malignant and invasive phenotypes along their interactions with astrocytes.

Lipid droplet biogenesis and COX-2 pathway activation are triggered by Barrett's esophagus and adenocarcinoma, but not esophageal squamous cell carcinoma risk factors.

Esophageal cancer (EC) is an aggressive disease, presenting two main histological subtypes: adenocarcinoma (EAC) and squamous cell carcinoma (ESCC). The two EC subtypes widely differ concerning virtually all factors. ESCC development is mainly associated with tobacco and alcohol abuse, whereas obesity and chronic gastroesophageal reflux disease (GERD) are important risk factors not only for EAC, but also for for Barrett's esophagus (BE), an intestinal metaplasia that precedes EAC.

P2Y receptor activation promotes esophageal cancer cells proliferation via ERK1/2 pathway.

Esophageal cancer is a prominent worldwide illness that is divided into two main subtypes: esophageal squamous cell carcinoma and esophageal adenocarcinoma. Mortality rates are alarming, and the understanding of the mechanisms involved in esophageal cancer development, becomes essential. Purinergic signaling is related to many diseases and among these various types of tumors.

Interplay between HMGA and TP53 in cell cycle control along tumor progression.

The high mobility group A (HMGA) proteins are found to be aberrantly expressed in several tumors. Studies (in vitro and in vivo) have shown that HMGA protein overexpression has a causative role in carcinogenesis process. HMGA proteins regulate cell cycle progression through distinct mechanisms which strongly influence its normal dynamics along malignant transformation.

High infiltration of B cells in tertiary lymphoid structures, TCR oligoclonality, and neoantigens are part of esophageal squamous cell carcinoma microenvironment.

Esophageal squamous cell carcinoma (ESCA) exhibits high intratumoral molecular heterogeneity posing a challenge to cancer therapy. Immune checkpoint blockade therapy has been approved for this disease, but with modest results. RNA-Seq data from paired tumor and surrounding nonmalignant tissue from 14 patients diagnosed with ESCA without previous treatment and from The Cancer Genome Atlas-ESCA cohort were analyzed.

Hpv impact on oropharyngeal cancer patients treated at the largest cancer center from Brazil.

Oropharyngeal squamous cell carcinoma (OSCC) is a fatal and highly incident disease. Although tobacco and alcohol consumption are the main risk factors associated with OSCC, a recent significant increase in OSCC HPV16 positive cases in high-income countries has been observed. However, it is not clear whether this change is also present in low- and middle-income countries.

Transcriptome Analysis Identifies ALCAM Overexpression as a Prognosis Biomarker in Laryngeal Squamous Cell Carcinoma.

Background: Laryngeal squamous cell carcinoma (LSCC) is one of the most incident tumors in the world, especially in developing countries, such as Brazil. Different from other tumors, LSCC prognosis did not improve during the past four decades. Therefore, the objective of this study was to develop biomarkers that can predict LSCC patient's prognosis.

Esophageal Cancer Development: Crucial Clues Arising from the Extracellular Matrix.

In the last years, the extracellular matrix (ECM) has been reported as playing a relevant role in esophageal cancer (EC) development, with this compartment being related to several aspects of EC genesis and progression. This sounds very interesting due to the complexity of this highly incident and lethal tumor, which takes the sixth position in mortality among all tumor types worldwide. The well-established increase in ECM stiffness, which is able to trigger mechanotransduction signaling, is capable of regulating several malignant behaviors by converting alteration in ECM mechanics into cytoplasmatic biochemical signals.

Multi-cancer V-ATPase molecular signatures: A distinctive balance of subunit C isoforms in esophageal carcinoma.

Background: V-ATPases are hetero-oligomeric enzymes consisting of 13 subunits and playing key roles in ion homeostasis and signaling. Differential expression of these proton pumps has been implicated in carcinogenesis and metastasis. To elucidate putative molecular signatures underlying these phenomena, we evaluated the expression of V-ATPase genes in esophageal squamous cell carcinoma (ESCC) and extended the analysis to other cancers.

The Prominent Role of HMGA Proteins in the Early Management of Gastrointestinal Cancers.

GI tumors represent a heterogeneous group of neoplasms concerning their natural history and molecular alterations harbored. Nevertheless, these tumors share very high incidence and mortality rates worldwide and patients' poor prognosis. Therefore, the identification of specific biomarkers could increase the development of personalized medicine, in order to improve GI cancer management.

Overexpression of Figures as a Potential Prognostic Factor in Endometrioid Endometrial Carcinoma (EEC).

Endometrioid endometrial carcinomas (EEC) are the most common malignant gynecologic tumors. Despite the increase in EEC molecular knowledge, the identification of new biomarkers involved in disease's development and/or progression would represent an improvement in its course. High-mobility group A protein (HMGA) family members are frequently overexpressed in a wide range of malignancies, correlating with a poor prognosis.

Regulation Is in the Air: The Relationship between Hypoxia and Epigenetics in Cancer.

Hypoxia is an inherent condition of tumors and contributes to cancer development and progression. Hypoxia-inducible factors (HIFs) are the major transcription factors involved in response to low O₂ levels, orchestrating the expression of hundreds of genes involved in cancer hallmarks' acquisition and modulation of epigenetic mechanisms. Epigenetics refers to inheritable mechanisms responsible for regulating gene expression, including genes involved in the hypoxia response, without altering the sequence of DNA bases.

Cell Cycle Progression Regulates Biogenesis and Cellular Localization of Lipid Droplets.

Intracellular lipid accumulation has been associated with a poor prognosis in cancer. We have previously reported the involvement of lipid droplets in cell proliferation in colon cancer cells, suggesting a role for these organelles in cancer development. In this study, we evaluate the role of lipid droplets in cell cycle regulation and cellular transformation.