Investigating the genetic makeup of the major histocompatibility complex (MHC) in the United Arab Emirates population through next-generation sequencing.

The Human leukocyte antigen (HLA) molecules are central to immune response and have associations with the phenotypes of various diseases and induced drug toxicity. Further, the role of HLA molecules in presenting antigens significantly affects the transplantation outcome. The objective of this study was to examine the extent of the diversity of HLA alleles in the population of the United Arab Emirates (UAE) using Next-Generation Sequencing methodologies and encompassing a larger cohort of individuals.

The Lund Molecular Taxonomy Applied to Non-Muscle-Invasive Urothelial Carcinoma.

The precise classification of tumors into relevant molecular subtypes will facilitate both future research and optimal treatment. Here, the Lund Taxonomy system for molecular classification of urothelial carcinoma was applied to two large and independent cohorts of non-muscle-invasive tumors. Of 752 tumors classified, close to 100% were of the luminal subtypes, 95% urothelial-like (Uro; UroA, UroB, or UroC) and 5% genomically unstable.

Molecular pathology of the non-luminal Ba/Sq-like and Sc/NE-like classes of urothelial tumours: An integrated immunohistochemical analysis.

Several groups have during past years produced molecular classification schemes for bladder cancer. Even though no consensus on how to define a subtype exists, one approach has been to base definitions on how tumours cluster according to their mRNA expression profiles. In many cases, obtained profiles, and thus class defining features, are affected by signals from non-tumour cells within the biopsy.

Stage-stratified molecular profiling of non-muscle-invasive bladder cancer enhances biological, clinical, and therapeutic insight.

Understanding the molecular determinants that underpin the clinical heterogeneity of non-muscle-invasive bladder cancer (NMIBC) is essential for prognostication and therapy development. Stage T1 disease in particular presents a high risk of progression and requires improved understanding. We present a detailed multi-omics study containing gene expression, copy number, and mutational profiles that show relationships to immune infiltration, disease recurrence, and progression to muscle invasion.

A comparison of rule-based and centroid single-sample multiclass predictors for transcriptomic classification.

Motivation: Gene expression-based multiclass prediction, such as tumor subtyping, is a non-trivial bioinformatic problem. Most classifier methods operate by comparing expression levels relative to other samples. Methods that base predictions on the expression pattern within a sample have been proposed as an alternative.

Different Responses to Neoadjuvant Chemotherapy in Urothelial Carcinoma Molecular Subtypes.

Background: For muscle-invasive bladder cancer (MIBC), no tissue biomarkers are available for clinical use to predict response to neoadjuvant chemotherapy.

Objective: To investigate how molecular subtypes impact pathological response and survival in patients receiving preoperative cisplatin-based chemotherapy.

Design, Setting, And Participants: Classification of a retrospective cohort of 149 patients was performed by tumor transcriptomic profiling and immunostaining.

multiclassPairs: an R package to train multiclass pair-based classifier.

Motivation: k-Top Scoring Pairs (kTSP) algorithms utilize in-sample gene expression feature pair rules for class prediction, and have demonstrated excellent performance and robustness. The available packages and tools primarily focus on binary prediction (i.e.

Recurring urothelial carcinomas show genomic rearrangements incompatible with a direct relationship.

We used the fact that patients with non-muscle invasive bladder tumors show local recurrences and multiple tumors to study re-initiation of tumor growth from the same urothelium. By extensive genomic analyses we show that tumors from the same patient are clonal. We show that gross genomic chromosomal aberrations may be detected in one tumor, only to be undetected in a recurrent tumor.

Molecular changes during progression from nonmuscle invasive to advanced urothelial carcinoma.

Molecular changes occurring during invasion and clinical progression of cancer are difficult to study longitudinally in patient-derived material. A unique feature of urothelial bladder cancer (UBC) is that patients frequently develop multiple nonmuscle invasive tumors, some of which may eventually progress to invade the muscle of the bladder wall. Here, we use a cohort of 73 patients that experienced a total of 357 UBC diagnoses to study the stability or change in detected molecular alterations during cancer progression.

Molecular pathology of the luminal class of urothelial tumors.

Molecular subtypes of urothelial carcinoma may be divided into luminal and nonluminal tumors. Nonluminal tumors are composed of cases with basal/squamous-like or small cell/neuroendocrine features, with a consensus on the molecular characteristics of the respective subtype. In contrast, luminal tumors are more disparate with three to five suggested subtypes and with definitions that do not always cohere.

Activin receptor-like kinase 1 is associated with immune cell infiltration and regulates CLEC14A transcription in cancer.

Cancer cells sustain their metabolic needs through nutrients and oxygen supplied by the bloodstream. The requirement for tumor angiogenesis has been therapeutically exploited in the clinical setting mainly by means of inhibition of the vascular endothelial growth factor family of ligands and receptors. Despite promising results in preclinical models, the benefits for patients proved to be limited.

Low Frequency of Intratumor Heterogeneity in Bladder Cancer Tissue Microarrays.

Background: Intratumoral heterogeneity (ITH) is associated with clinical challenges such as possible differences in response to treatment and difficulties in classifying the tumor. Previously, ITH has been described in bladder cancer using detailed genetic analyses. However, in this disease, it is not known to what extent ITH actually occurs, or if it involves molecular subtyping, when assessment is achieved by immunohistochemistry (IHC) on the protein level using tissue microarrays (TMAs), the method most widely applied when analyzing large sample numbers.

Discordant molecular subtype classification in the basal-squamous subtype of bladder tumors and matched lymph-node metastases.

Molecular subtypes of muscle-invasive bladder tumors have emerged as a promising research tool with potential to stratify patients for neoadjuvant treatment. Prior to radical cystectomy, the utility of molecular classification and biomarkers depend on concordance between tissue from transurethrally resected specimens and disseminated disease. We assess the concordance of molecular subtypes and a large number of potential biomarkers in 67 pairs of muscle-invasive bladder tumors and synchronous lymph-node metastases.

A validation and extended description of the Lund taxonomy for urothelial carcinoma using the TCGA cohort.

Global gene expression analysis has been a major tool for urothelial carcinoma subtype discovery. This approach has revealed extensive complexity both in intrinsic features of the tumor cells and in the microenvironment. However, global gene expression cannot distinguish between gene expression signals originating from the tumor cells proper and from normal cells in the biopsy.

Clinical Characteristics and Risk Factors of Extensive Macular Atrophy with Pseudodrusen: The EMAP Case-Control National Clinical Trial.

Purpose: To assess the association of clinical and biological factors with extensive macular atrophy with pseudodrusen (EMAP) characterized by bilateral macular atrophy occurring in patients aged 50 to 60 years and a rapid progression to legal blindness within 5 to 10 years.

Design: A national matched case-control study.

Participants: Participants were recruited in 10 French Departments of Ophthalmology and their associated clinical investigation centers.

CopyNumber450kCancer: baseline correction for accurate copy number calling from the 450k methylation array.

Unlabelled: The Illumina Infinium HumanMethylation450 BeadChip (450k) is widely used for the evaluation of DNA methylation levels in large-scale datasets, particularly in cancer. The 450k design allows copy number variant (CNV) calling using existing bioinformatics tools. However, in cancer samples, numerous large-scale aberrations cause shifting in the probe intensities and thereby may result in erroneous CNV calling.

Homozygosity mapping in autosomal recessive retinitis pigmentosa families detects novel mutations.

Purpose: Autosomal recessive retinitis pigmentosa (arRP) is a genetically heterogeneous disease resulting in progressive loss of photoreceptors that leads to blindness. To date, 36 genes are known to cause arRP, rendering the molecular diagnosis a challenge. The aim of this study was to use homozygosity mapping to identify the causative mutation in a series of inbred families with arRP.

Variants in PTPN22 and SMOC2 genes and the risk of thyroid disease in the Jordanian Arab population.

Autoimmune thyroid diseases (AITDs) (Hashimoto thyroiditis and Graves' disease) are complex polygenic disorders with multiple genes thought to contribute to the risk of disease. The contribution of these genes differs by different populations. The PTPN22 gene is reported to be associated with multiple autoimmune diseases, but results of association are conflicting in different populations.

SMOC2 gene variant and the risk of vitiligo in Jordanian Arabs.

Generalized vitiligo is a common autoimmune disorder, characterized by patchy loss of pigmentation due to melanocyte death. It is a multifactorial disorder in which multiple genes and environmental triggers contribute to the expression of the phenotype. Different genetic variants can have varying effects on having vitiligo.