Context-dependent effects of CDKN2A and other 9p21 gene losses during the evolution of esophageal cancer.

CDKN2A is a tumor suppressor located in chromosome 9p21 and frequently lost in Barrett's esophagus (BE) and esophageal adenocarcinoma (EAC). How CDKN2A and other 9p21 gene co-deletions affect EAC evolution remains understudied. We explored the effects of 9p21 loss in EACs and cancer progressor and non-progressor BEs with matched genomic, transcriptomic and clinical data.

Novel Transcriptional and DNA Methylation Abnormalities of SORT1 Gene in Non-Small Cell Lung Cancer.

Sortilin is an important regulator with potential tumour-suppressor function by limiting EGFR signalling. In this study, we undertook a comprehensive expression analysis of sortilin transcript variants and the DNA methylation status of their corresponding promoters in human non-small cell carcinomas (NSCLCs). RNA/DNA was extracted from 81 NSCLC samples and paired normal tissue.

A SIMPLI (Single-cell Identification from MultiPLexed Images) approach for spatially-resolved tissue phenotyping at single-cell resolution.

Multiplexed imaging technologies enable the study of biological tissues at single-cell resolution while preserving spatial information. Currently, high-dimension imaging data analysis is technology-specific and requires multiple tools, restricting analytical scalability and result reproducibility. Here we present SIMPLI (Single-cell Identification from MultiPLexed Images), a flexible and technology-agnostic software that unifies all steps of multiplexed imaging data analysis.

Comparative assessment of genes driving cancer and somatic evolution in non-cancer tissues: an update of the Network of Cancer Genes (NCG) resource.

Background: Genetic alterations of somatic cells can drive non-malignant clone formation and promote cancer initiation. However, the link between these processes remains unclear and hampers our understanding of tissue homeostasis and cancer development.

Results: Here, we collect a literature-based repertoire of 3355 well-known or predicted drivers of cancer and non-cancer somatic evolution in 122 cancer types and 12 non-cancer tissues.

Clone competition as a mechanism to reduce tumor formation.

With age, clones carrying somatic mutations in well-known cancer driver genes progressively populate adult tissues, yet cancer transformation is rare. In a recent issue of Nature, Colom et al. showed that competition between mutated clones with different fitness could act as a tumor-protective mechanism.

Immunogenomics of Colorectal Cancer Response to Checkpoint Blockade: Analysis of the KEYNOTE 177 Trial and Validation Cohorts.

Background & Aims: Colorectal cancer (CRC) shows variable response to immune checkpoint blockade, which can only partially be explained by high tumor mutational burden (TMB). We conducted an integrated study of the cancer tissue and associated tumor microenvironment (TME) from patients treated with pembrolizumab (KEYNOTE 177 clinical trial) or nivolumab to dissect the cellular and molecular determinants of response to anti- programmed cell death 1 (PD1) immunotherapy.

Methods: We selected multiple regions per tumor showing variable T-cell infiltration for a total of 738 regions from 29 patients, divided into discovery and validation cohorts.

Transcriptome Profiling Reveals New Insights into the Immune Microenvironment and Upregulation of Novel Biomarkers in Metastatic Uveal Melanoma.

Metastatic uveal melanoma (mUM) to the liver is incurable. Transcriptome profiling of 40 formalin-fixed paraffin-embedded mUM liver resections and 6 control liver specimens was undertaken. mUMs were assessed for morphology, nuclear BAP1 (nBAP1) expression, and their tumour microenvironments (TME) using an "immunoscore" (absent/altered/high) for tumour-infiltrating lymphocytes (TILs) and macrophages (TAMs).

Balancing neurotrophin pathway and sortilin function: Its role in human disease.

Neurotensin receptor-3 or sortilin is a vacuolar protein sorting 10 protein domain (Vps10p) has been firstly discovered in the human brain, it acts as receptor or co-receptor of the cell and traffics different proteins within the cell. Sortilin deregulation contributes to the development of several diseases, including neurological diseases and cancer. On the other hand, neurotrophins which are a family of proteins essential for the nervous system development, function and plasticity.

Piloting a Deep Learning Model for Predicting Nuclear BAP1 Immunohistochemical Expression of Uveal Melanoma from Hematoxylin-and-Eosin Sections.

Background: Uveal melanoma (UM) is the most common primary intraocular malignancy in adults. Monosomy 3 and mutation are strong prognostic factors predicting metastatic risk in UM. Nuclear BAP1 (nBAP1) expression is a close immunohistochemical surrogate for both genetic alterations.

Overexpression of mRNA in head and neck carcinoma and association with response to vinorelbine.

gene encodes the hepatoma upregulated protein (HURP), a microtubule associated protein regulating mitotic spindle dynamics, which promotes chromosomal congression and alignment during mitosis, with a potential role in tumorigenesis. In the present study, mRNA expression was investigated by reverse transcription-quantitative PCR in oropharyngeal squamous cell carcinoma (OPSCC). Primary OPSCC tumors from 107 patients and 48 adjacent normal tissues, as well as 12 respiratory tract cancer cell lines (9 head and neck squamous cell carcinoma, 2 lung cancer and 1 normal bronchial) were utilised in the present study.

Long non-coding RNA dysregulation is a frequent event in non-small cell lung carcinoma pathogenesis.

Background: Long non-coding RNAs compose an important level of epigenetic regulation in normal physiology and disease. Despite the plethora of publications of lncRNAs in human cancer, the landscape is still unclear.

Methods: Microarray analysis in 44 NSCLC paired specimens was followed by qPCR-based validation in 29 (technical) and 38 (independent) tissue pairs.

Oral Candida colonization in patients with chronic periodontitis. Is there any relationship?

Background: Candida can be implicated in the pathology of chronic periodontitis.

Aims: To analyze the oral Candida carriage in patients suffering from chronic periodontitis (CP) and its correlation with the severity of this condition.

Methods: Microbiological samples were taken from 155 patients using the oral rinse (OR) technique and by using paper points in the periodontal pockets (GPP).

Development and validation of molecular methodologies to assess PALB2 expression in sporadic breast cancer.

Objectives: Recent reports have included PALB2 (Partner and localizer of BRCA2) in the growing list of hereditary cancer genes. PALB2 mutations confer a moderate breast cancer risk in heterozygotes and Fanconi anemia in biallelic mutation carriers. PALB2 protein co-localizes with BRCA2 and BRCA1 in nuclear structures and enables error-free homologous recombination repair of double-stranded DNA breaks.

Polymorphisms in alcohol and tobacco metabolism genes in head and neck cancer in the Basque Country.

Background: The Basque Country has one of the highest rates of head and neck squamous cell carcinoma (HNSCC) in Europe, although tobacco and alcohol consumption are not high when compared to other European countries where HNSCC incidence is lower. Our aim was to determine the role of genetic variation with regard to the metabolism of alcohol and carcinogens from tobacco smoke in the Basque Country.

Methods: Fourteen polymorphisms in alcohol or tobacco metabolism genes were genotyped in 84 HNSCC patients and 242 healthy individuals from the Basque Country.

Role of cytochrome P-450 genetic polymorphisms in oral carcinogenesis.

Oral cancer is one of the most frequent head and neck cancers, and epidemiological studies have shown that smoking is a major risk factor in this pathology. However, as not all smokers develop oral cancer, some individuals must be more susceptible to develop this disease. This individual susceptibility has been related to different genetic variants in metabolizing enzymes.

DNA methylation epigenotypes in breast cancer molecular subtypes.

Introduction: Identification of gene expression based breast cancer subtypes is considered as a critical means of prognostication. Genetic mutations along with epigenetic alterations contribute to gene expression changes occurring in breast cancer. So far, these epigenetic contributions to sporadic breast cancer subtypes have not been well characterized, and there is only a limited understanding of the epigenetic mechanisms affected in those particular breast cancer subtypes.

Oral cancer and polymorphism of ethanol metabolising genes.

Oral cancer is the sixth most common cancer worldwide and a major health problem in some parts of the world. Epidemiological studies have shown that habitual alcohol consumption could be a risk factor in oral carcinogenesis, although the true involvement of alcohol is unknown. Via alcohol dehydrogenase (ADH) and cytochrome P450 oxidase (CYP) alcohol is metabolized to acetaldehyde, a highly toxic compound, which plays an important role in carcinogenesis.

p53 mutation is rare in oral mucosa brushings from patients previously treated for a head and neck squamous cell carcinoma.

Mutations of the tumour suppressor gene p53 are common in human cancer, and seem to be an early event in head and neck squamous cell carcinomas. The aim of our study was to determine the status of the tumour suppressor gene p53 in the oral mucosa of patients previously treated for a head and neck squamous cell carcinoma, at risk of developing an oral squamous cell carcinoma, but without oral clinical lesions. Oral brushings from 87 patients were sequenced with matched genomic DNA.

Gorlin-Goltz syndrome: clinicopathologic aspects.

Gorlin-Goltz syndrome, also known as nevoid basal cell carcicoma syndrome, comes into being due to a genetic alteration produced by a mutation in the "Patched" tumour suppressor gene, and it is inherited in a dominant autosomal way, though sporadic cases have been found. This syndrome shows a high penetrance and variable expressiveness. It is about a multisystemic process that is characterised by the presence of multiple pigmented basocellular carcinomas, keratocysts in the jaws, palmar and/or plantar pits and calcification of the falxcerebri.

p16(INK4a) promoter hypermethylation in oral scrapings of oral squamous cell carcinoma risk patients.

Aberrant promoter hypermethylation is common in oral squamous cell carcinoma (OSCC) and may be useful as a marker for cancer cells. The aim of our study was to assess whether the detection of hypermethylation of the promoter region of p16(INK4a) in oral cytological samples could be a marker in patients with risk of developing an OSCC. Hypermethylation was detected in 20% (29/145) of the cases analyzed.