Keratins are a diverse group of structural proteins that form the intermediate filament network responsible for maintaining the structural integrity of keratinocytes. In humans, there are around 30 keratin families divided into two groups, namely, acidic and basic keratins, which are arranged in pairs. They are expressed in a highly specific pattern related to the epithelial type and stage of cellular differentiation. A total of 54 functional genes exist which codes for these keratin families. The expression of specific keratin genes is regulated by the differentiation of epithelial cells within the stratifying squamous epithelium. Mutations in most of these genes are now associated with specific tissue fragility disorders which may manifest both in skin and mucosa depending on the expression pattern. The keratins and keratin-associated proteins are useful as differentiation markers because their expression is both region specific and differentiation specific. Antibodies to keratin are considered as important tissue differentiation markers and therefore are an integral aid in diagnostic pathology. The present review discusses the structure of keratin, the various types of keratin and their distribution and the disorders associated with keratinization with special emphasis on the disorders of the oral cavity. A brief note on the clinical significance of keratin is also mentioned.
We developed and characterized a next-generation sequencing (NGS) technology for streamlined analysis of DNA and RNA using low-input, low-quality cancer specimens. A single-workflow, targeted NGS panel for non–small cell lung cancer (NSCLC) was designed covering 135 RNA and 55 DNA disease-relevant targets. This multiomic panel was used to assess 219 formalin-fixed paraffin-embedded NSCLC surgical resections and core needle biopsies. Mutations and expression phenotypes were identified consistent with previous large-scale genomic studies, including mutually exclusive DNA and RNA oncogenic driver events. Evaluation of a second cohort of low cell count fine-needle aspirate smears from the BATTLE-2 trial yielded 97% agreement with an independent, validated NGS panel that was used with matched surgical specimens. Collectively, our data indicate that broad, clinically actionable insights that previously required independent assays, workflows, and analyses to assess both DNA and RNA can be conjoined in a first-tier, highly multiplexed NGS test, thereby providing faster, simpler, and more economical results.
Lung cancer accounts for approximately 14% of all newly diagnosed cancers and is the leading cause of cancer-related deaths. Chimeric RNA resulting from gene fusions (RNA fusions) and other RNA splicing errors are driver events and clinically addressable targets for nonesmall cell lung cancer (NSCLC). The reliable assessment of these RNA markers by next-generation sequencing requires integrated reagents, protocols, and interpretive software that can harmonize procedures and ensure consistent results across laboratories. We describe the development and verification of a system for targeted RNA sequencing for the analysis of challenging, low-input solid tumor biopsies that includes reagents for nucleic acid quantification and library preparation, run controls, and companion bioinformatics software. Assay development reconciled sequence discrepancies in public databases, created predictive formalin-fixed, paraffin-embedded RNA qualification metrics, and eliminated read misidentification attributable to index hopping events on the next-generation sequencing flow cell. The optimized and standardized system was analytically verified internally and in a multiphase study conducted at five independent laboratories. The results show accurate, reproducible, and sensitive detection of RNA fusions, alternative splicing events, and other expression markers of NSCLC. This comprehensive approach, combining sample quantification, quality control, library preparation, and interpretive bioinformatics software, may accelerate the routine implementation of targeted RNA sequencing of formalin-fixed, paraffin-embedded samples relevant to NSCLC.
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