Common Precursor Research Articles

Novel hydroxy-tagged bis-dihydrazothiazole derivatives: Synthesis, antimicrobial capacity and formation of some metal chelates with iron, cobalt and zinc ions

Until today, microbialinfectionsepitomize a seriousuniversal health threat. Subsequently, developing a potential antimicrobialprototype remains an urgent, global necessity. Despite several reports discussing the biological utility of some bis-thiazoles, the use of bis-dihydrazothiazoles and their corresponding metal chelates as potent antimicrobials, is yet to be explored. The current report outlines an attempt to fill that void by representing a successful synthesis of a new class of bis-dihydrazothiazoles as well as three of their transition metal chelates and their use as potential antimicrobials. This report presents the design of some novel hydroxy-tagged bis-dihydrazothiazoles 6a-e and bis-dihydrazothiazolones 9a-evia the reaction of a bis-aldehyde thiosemicarbazone 3, as a common synthetic precursor, with two groups of hydrazonoyl halide derivatives 4a-e and 7a-e. The chelation affinity of these novel bis-dihydrazothiazoles to behave as neutral tridentate ligands coordinating to the metal ions; Fe(III), Co(II), or Zn(II) through azomethine-N, thiazole-S, and azo-N atoms to form metal complexes with a metal/ligand ratio of 2:1 was confirmed. In-vitro, antimicrobial screening of the novel hydroxy-tagged bis-dihydrazothiazole derivatives, as well as a selected group of their transition metal chelate complexes [M2L], was inspected, and the data weremeasured incomparisonto those of ketoconazole and gentamycin as antimicrobial reference standards. Most bis-dihydrazothiazoles 6a-e and bis-dihydrazothiazolones 9a-e showed decent to excellent antimicrobial activities against the screened microbes, but the chloro-substituted bis dihydrazothiazole derivatives 6c and 9c showed exceptional inhibition of Bacillus subtilis (20 mm), Escherichia coli (25 mm), and Candida albicans (19 mm), and Salmonella typhimurium (19 mm), respectively. Additionally, amongst the three synthesized metal complexes [M2L], only the zinc complex, [Zn2L] showed remarkable inhibition of both Staphylococcus aureus (21 mm) and Salmonella typhimurium (19 mm) compared to the reference standard Gentamycin, and was more potent than the free ligand, 6a itself (no activity and 11 mm respectively). Antimicrobial inspection was assessed by the agar well diffusion assay method against all bacterial and fungal strains. Magnetic moment, diffused reflectance, FT-IR, 1H NMR, molar conductivity, thermogravimetric analysis (TGA), X-ray diffraction (XRD), and scanning electron microscope(SEM) were among the many techniques used to elucidate the structures of all novel hydroxy-tagged bis-heterocyclic ligands and their metal chelate complexes.

The Pigment World: Life's Origins as Photon-Dissipating Pigments.

Many of the fundamental molecules of life share extraordinary pigment-like optical properties in the long-wavelength UV-C spectral region. These include strong photon absorption and rapid (sub-pico-second) dissipation of the induced electronic excitation energy into heat through peaked conical intersections. These properties have been attributed to a "natural selection" of molecules resistant to the dangerous UV-C light incident on Earth's surface during the Archean. In contrast, the "thermodynamic dissipation theory for the origin of life" argues that, far from being detrimental, UV-C light was, in fact, the thermodynamic potential driving the dissipative structuring of life at its origin. The optical properties were thus the thermodynamic "design goals" of microscopic dissipative structuring of organic UV-C pigments, today known as the "fundamental molecules of life", from common precursors under this light. This "UV-C Pigment World" evolved towards greater solar photon dissipation through more complex dissipative structuring pathways, eventually producing visible pigments to dissipate less energetic, but higher intensity, visible photons up to wavelengths of the "red edge". The propagation and dispersal of organic pigments, catalyzed by animals, and their coupling with abiotic dissipative processes, such as the water cycle, culminated in the apex photon dissipative structure, today's biosphere.

Big is beautiful: Health and well‐being in Pacific communities

AbstractResearch on obesity and its implications for health and well‐being has been a global focus. However, this examination has often overlooked the unique perspective of intracultural Pasifika communities. In New Zealand, Pacific Islanders are one such community. For Pasifika diaspora communities, obesity is a common precursor to poor health outcomes. As a result, my research has honed in on the social, cultural, and economic factors contributing to obesity in these cohorts. The practical implications of this study underscore the urgent need for culturally sensitive intervention programs that respect and work within the cultural norms of these communities aimed at alleviating this condition. This emphasis on cultural sensitivity is crucial for understanding and addressing the issue. My research delves into the emic perceptions of what “Big” entails, particularly within intracultural Pasifika communities. I explore contemporary conceptions and their implications for health and well‐being. I argue that Pasifika churches, as socio‐cultural villages, have the potential to transform into safe, healthy spaces for their people. This transformation could significantly reduce the prevalence of an obesogenic environment and contribute to improved mental and physical health for the population. This optimistic perspective, which highlights the potential for positive change, guides my exploration of a relevant recommendation for the issue at hand.

Assessment of wafer scale MoS2 atomic layers grown by metal-organic chemical vapor deposition using organo-metal, organo-sulfide, and H2S precursors.

Transition Metal Dichalcogenides (TMDs) are a unique class of materials that exhibit attractive electrical and optical properties which have generated significant interest for applications in microelectronics, optoelectronics, energy storage, and sensing. Considering the potential of these materials to impact such applications, it is crucial to develop a reliable and scalable synthesis process that is compatible with modern industrial manufacturing methods. Metal-organic chemical vapor deposition (MOCVD) offers an ideal solution to produce TMDs, due to its compatibility with large-scale production, precise layer control, and high material purity. Optimization of MOCVD protocols is necessary for effective TMD synthesis and integration into mainstream technologies. Additionally, improvements in metrology are necessary to measure the quality of the fabricated samples more accurately. In this work, we study MOCVD of wafer-scale molybdenum disulfide (MoS2) utilizing two common chalcogen precursors, H2S and DTBS. We then develop a metrology platform for wafer scale samples quality assessment. For this, the coalesced films were characterized using Raman spectroscopy, atomic force microscopy, transmission electron microscopy, X-ray photoelectron spectroscopy, and Kelvin probe force microscopy. We then correlate the structural analysis of these grown films with electrical performance by using aerosol jet printing to fabricate van der Pauw test structures and assess sheet resistance.

Iodine Clusters in the Atmosphere I: Computational Benchmark and Dimer Formation of Oxyacids and Oxides.

The contribution of iodine-containing compounds to atmospheric new particle formation is still not fully understood, but iodic acid and iodous acid are thought to be significant contributors. While several quantum chemical studies have been carried out on clusters containing iodine, there is no comprehensive benchmark study quantifying the accuracy of the applied methods. Here, we present the first study in a series that investigate the role of iodine species in atmospheric cluster formation. In this work, we have studied the iodic acid, iodous acid, iodine tetroxide, and iodine pentoxide monomers and their dimers formed with common atmospheric precursors. We have tested the accuracy of commonly applied methods for calculating the geometry of the monomers, thermal corrections of monomers and dimers, the contribution of spin-orbit coupling to monomers and dimers, and finally, the accuracy of the electronic energy correction calculated at different levels of theory. We find that optimizing the structures either at the ωB97X-D3BJ/aug-cc-pVTZ-PP or the M06-2X/aug-cc-pVTZ-PP level achieves the best thermal contribution to the binding free energy. The electronic energy correction can then be calculated at the ZORA-DLPNO-CCSD(T0) level with the SARC-ZORA-TZVPP basis for iodine and ma-ZORA-def2-TZVPP for non-iodine atoms. We applied this methodology to calculate the binding free energies of iodine-containing dimer clusters, where we confirm the qualitative trends observed in previous studies. However, we identify that previous studies overestimate the stability of the clusters by several kcal/mol due to the neglect of relativistic effects. This means that their contributions to the currently studied nucleation pathways of new particle formation are likely overestimated.

Nitrogen-doped carbon dots as efficient turn-on fluorescent probe for assay of organophosphorus pesticides

Concerns regarding human health and food safety have generated interest in developing simple, accurate, and cost-effective strategies for evaluating organophosphorus pesticide (OP) residues. In this study, nitrogen-doped carbon dots (N-CDs) were synthesized from a common low-cost precursor via a simple pyrolysis process. The fluorescence of the N-CDs can be suppressed by p-nitrophenol, which is the hydrolysis product of the p-nitrophenyl phosphate salt catalyzed by alkaline phosphatase (ALP). A fluorescent turn-on assay for the inhibitory effect of glyphosate was developed with a low detection limit and wide linear range. Moreover, the feasibility of visualizing OPs in vegetables was demonstrated by the fluorescence imaging of glyphosate on cabbage leaves. This research not only offers a facile method for the synthesis of highly fluorescent CDs but also inspires the development of effective multi-mode sensing platforms that include fluorescent testing and imaging for monitoring pesticide residues.

Construction of the Akuammiline Alkaloid Core Structure via Stereoselective E-Ring Formation.

Construction of the core structure of akuammiline alkaloids with three-dimensional cage-like structures for their diversity-oriented synthesis was investigated. Extensive exploration centered around the introduction of nitrogen functional groups and construction of the E-ring in an intramolecular or intermolecular manner revealed that a Claisen rearrangement approach involving intramolecular amination provided a common precursor, potentially facilitating divergent access to various types of akuammiline alkaloids.

Interconnected lineage trajectories link conventional and natural killer (NK)-like exhausted CD8+ T cells beneficial in type 1 diabetes

Distinct Natural Killer (NK)-like CD57+ and PD-1+ CD8+ exhausted-like T cell populations (Tex) have both been linked to beneficial immunotherapy response in autoimmune type 1 diabetes (T1D) patients. The origins and relationships between these cell types are poorly understood. Here we show that while PD-1+ and CD57+ Tex populations are epigenetically similar, CD57+ Tex cells display unique increased chromatin accessibility of inhibitory Killer Cell Immunoglobulin-like Receptor (iKIR) and other NK cell genes. PD-1+ and CD57+ Tex also show reciprocal expression of Inhibitory Receptors (IRs) and iKIRs accompanied by chromatin accessibility of Tcf1 and Tbet transcription factor target sites, respectively. CD57+ Tex show unappreciated gene expression heterogeneity and share clonal relationships with PD-1+ Tex, with these cells differentiating along four interconnected lineage trajectories: Tex-PD-1+, Tex-CD57+, Tex-Branching, and Tex-Fluid. Our findings demonstrate new relationships between Tex-like populations in human autoimmune disease and suggest that modulating common precursor populations may enhance response to autoimmune disease treatment.

Associations of amyloid-β oligomers and plaques with neuropathology in the App NL-G-F mouse.

Amyloid-β pathology and neurofibrillary tangles lead to glial activation and neurodegeneration in Alzheimer's disease. In this study, we investigated the relationships between the levels of amyloid-β oligomers, amyloid-β plaques, glial activation and markers related to neurodegeneration in the App NL-G-F triple mutation mouse line and in a knock-in line homozygous for the common human amyloid precursor protein (App hu mouse). The relationships between neuropathological features were characterized with immunohistochemistry and imaging mass cytometry. Markers assessing human amyloid-β proteins, microglial and astrocytic activation and neuronal and synaptic densities were used in mice between 2.5 and 12 months of age. We found that amyloid-β oligomers were abundant in the brains of App hu mice in the absence of classical amyloid-β plaques. These brains showed morphological changes consistent with astrocyte activation but no evidence of microglial activation or synaptic or neuronal pathology. In contrast, both high levels of amyloid-β oligomers and numerous plaques accumulated in App NL-G-F mice in association with substantial astrocytic and microglial activation. The increase in amyloid-β oligomers over time was more strongly correlated with astrocytic than with microglia activation. Spatial analyses suggested that activated microglia were more closely associated with amyloid-β oligomers than with amyloid-β plaques in App NL-G-F mice, which also showed age-dependent decreases in neuronal and synaptic density markers. A comparative study of the two models highlighted the dependence of glial and neuronal pathology on the nature and aggregation state of the amyloid-β peptide. Astrocyte activation and neuronal pathology appeared to be more strongly associated with amyloid-β oligomers than with amyloid-β plaques, although amyloid-β plaques were associated with microglia activation.

Promoter dependent RNA polymerase II bypass of the epimerizable DNA lesion, Fapy•dG and 8-Oxo-2'-deoxyguanosine.

Formamidopyrimidine (Fapy•dG) is a major lesion arising from oxidation of dG that is produced from a common chemical precursor of 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-OxodGuo). In human cells, replication of single-stranded shuttle vectors containing Fapy•dG is more mutagenic than 8-OxodGuo. Here, we present the first data regarding promoter dependent RNA polymerase II bypass of Fapy•dG. 8-OxodGuo bypass was examined side-by-side. Experiments were carried out using double-stranded shuttle vectors in HeLa cell nuclear lysates and in HEK 293T cells. The lesions do not significantly block transcriptional bypass efficiency. Less than 2% adenosine incorporation occurred in cells when the lesions were base paired with dC. Inhibiting base excision repair in HEK 293T cells significantly increased adenosine incorporation, particularly from Fapy•dG:dC bypass which yielded ∼25% adenosine incorporation. No effect was detected upon transcriptional bypass of either lesion in nucleotide excision repair deficient cells. Transcriptional mutagenesis was significantly higher when shuttle vectors containing dA opposite one of the lesions were employed. For Fapy•dG:dA bypass, adenosine incorporation was greater than 85%; whereas 8-OxodGuo:dA yielded >20% point mutations. The combination of more frequent replication mistakes and greater error-prone Pol II bypass suggest that Fapy•dG is more mutagenic than 8-OxodGuo.

Mechanisms underlying the formation of main volatile odor sulfur compounds in foods during thermal processing.

Volatile sulfur compounds (VSCs) significantly influence food flavor and garner considerable attention in flavor research due to their low sensory thresholds, diverse odor attributes, and high reactivity. Extensive research studies have explored VSC formation through thermal processes such as the Maillard reaction, thermal pyrolysis, oxidation, and enzymatic reactions. However, understanding of the specific reaction mechanisms and processes remains limited. This is due to the dispersed nature of existing studies, the undefined intermediates involved, and the complexity of the matrices and processing conditions. Given these limitations, the authors have shifted their focus from foods to sulfides. The structure, source, and chemical characteristics of common precursors (sulfur-containing amino acids and derivatives, thiamine, thioglucoside, and lentinic acid) and their corresponding reactive intermediates (hydrogen sulfide, thiol, alkyl sulfide, alkyl sulfenic acid, and thial) are provided, and the degradation mechanisms, reaction rules, and matrix conditions are summarized based on their chemical characteristics. Additionally, the VSC formation processes in several typical foods during processing are elucidated, adhering to these identified rules. This article provides a comprehensive overview of VSCs, from precursors and intermediates to end products, and is crucial for understanding the mechanisms behind VSC formation and managing the flavor qualities of processed foods.

Metal-free advanced energy materials for the oxygen reduction reaction in anion-exchange membrane fuel cells

The success of the next generation of anion-exchange membrane fuel cells (AEMFCs) depends on the development of active, reliable, and economical oxygen reduction reaction (ORR) catalysts. Here, we synthesize a series of ultra-low-cost metal-free ORR catalysts by doping a common pristine graphite precursor with chemically singular-type heteroatoms, namely I, S, N, or B, using single-step planetary ball milling technique. All doped-graphites show substantially enhanced ORR performance relative to the pristine (undoped) graphite. Among all the tested catalysts, N-graphite exhibited the highest ORR onset potential of 0.87 V vs. reversible hydrogen electrode. These results are supported by density functional theory calculations. The ORR catalysts also exhibit remarkable stability as evaluated through electrochemical tests. Most importantly, the AEMFCs prepared using these ultra-low-cost doped graphites deliver notable peak power densities with impressive voltage efficiencies, which further supports their efficacy in ORR catalysis and the broad implementation of this technology.

The evolution of musicality and cross-domain co-evolutionary interactions

The evolution of human musicality has often been linked to the evolution of the faculty of language since the development of musical and linguistic abilities seems to share a common phase in their ontogenesis. Apart from that, both singing and speaking are, on the one hand, universal forms of human vocal expression and, on the other hand, consist of culturally specific elements. Such a probable co-occurrence of the predisposition to speak and sing, with the cultural variability of both these forms of communication, has prompted researchers to indicate gene–culture co-evolution as the probable mechanism responsible for the emergence of human musicality and the faculty of language. However, in most evolutionary scenarios proposed so far, the evolutionary paths of music and language followed independently after divergence from a common precursor. This article, based on observations of contemporary interactions between language and music, presents a different view in which musical and language-like forms of proto-communication interacted leading to the repurposing of some of their neural mechanisms. In this process, the Baldwinian interplay between plasticity and canalization has been proposed as the most probable evolutionary mechanism that shaped our musicality. The premises that support the presence of cross-domain co-evolutionary interactions in the contemporary communicative niche of Homo sapiens are indicated.

Distinct developmental pathways generate functionally distinct populations of natural killer cells.

Natural killer (NK) cells function by eliminating virus-infected or tumor cells. Here we identified an NK-lineage-biased progenitor population, referred to as early NK progenitors (ENKPs), which developed into NK cells independently of common precursors for innate lymphoid cells (ILCPs). ENKP-derived NK cells (ENKP_NK cells) and ILCP-derived NK cells (ILCP_NK cells) were transcriptionally different. We devised combinations of surface markers that identified highly enriched ENKP_NK and ILCP_NK cell populations in wild-type mice. Furthermore, Ly49H+ NK cells that responded to mouse cytomegalovirus infection primarily developed from ENKPs, whereas ILCP_NK cells were better IFNγ producers after infection with Salmonella and herpes simplex virus. Human CD56dim and CD56bright NK cells were transcriptionally similar to ENKP_NK cells and ILCP_NK cells, respectively. Our findings establish the existence of two pathways of NK cell development that generate functionally distinct NK cell subsets in mice and further suggest these pathways may be conserved in humans.

The various synergistic impacts of precursor emission reduction on PM2.5 and O3 in a typical industrial city with complex distributions of emissions

The synergistic responses of O3 and PM2.5 to their common precursors remain unclear within industrial cities with complex emissions. In this study, hundreds of scenarios of jointly reduced local NOx and VOCs emissions were designed along with the source apportionment techniques embedded in the Comprehensive Air quality Model with extensions (CAMx) system to explore the locally formed O3 and PM2.5 sensitivities to the reduced emissions of NOx and VOCs. The results indicate that locally formed O3 and PM2.5 are more connected to local emissions, resulting in unique formation sensitivities. Local O3 formation is usually in a transitional regime and transferred to VOC-limited condition under O3-polluted conditions due to high VOC emissions. Locally formed O3 and PM2.5 vary largely in different functional regions due to different emission feature and meteorological condition. When reducing VOCs emissions alone, an increase in PM2.5 formation could be observed due to the increase in the formation of nitrate resulting from reduced competition of NOx in O3 formation. To reduce PM2.5 and O3 concentrations simultaneously, specific ratios of NOx reduction percentage to VOC reduction percentage should be considered to different functional regions under different pollution levels. This research highlights the importance to conduct targeted sensitivity tests for emission reduction in different functional zones with complex emission features for the coordinated control of O3 and PM2.5 pollution in typical industrialized cities.

Cloning and functional characterization of oxidosqualene cyclase gene for α-amyrin synthesis

Ursolic acid has gradually attracted much attention due to its unique pharmacological activities and valuable market value in recent years. Currently, ursolic acid is mostly extracted from loquat leaves, but the plant extraction method has low yield and high cost, and chemical synthesis is not readily available, so the biosynthesis method provides a new source for ursolic acid. α-amyrin acts as the main precursor for the synthesis of ursolic acid, and its yield is positively correlated with ursolic acid yield. Oxidosqualene cyclase(OSC) belongs to a multigene family which can catalyze the common precursor 2,3-oxidosqualene to generate different types of triterpene backbones, and plays a decisive role in the synthesis of triterpenoids. However, there are fewer reported key genes catalyzing the synthesis of α-amyrin in medicinal plants, and the yield and proportion of α-amyrin in the catalyzed products have always been a focus of research. In this study, ItOSC2, MdOSC1, AaOSC2 and CrAS, four enzymes capable of catalyzing the production of α-amyrin from 2,3-oxidosqualene, were cloned from Iris tectorum, Malus domestica, Artemisia annua and Catharanthus roseus, subject to sequence alignment and phylogenetic tree analyses, and transformed into Saccharomyces cerevisiae as plasmids. After 7 days of fermentation, the yield and proportions of α-amyrin, β-amyrin and ergosterol were measured. Finally, AaOSC2 with the best ability to catalyze the generation of α-amyrin was filtered out, providing a key gene element for the later construction of engineered yeast strains with high production of α-amyrin and ursolic acid.

ScRNA-seq profiling of human granulocytes reveals expansion of developmentally flexible neutrophil precursors with mixed neutrophil and eosinophil properties in asthma.

Neutrophils and eosinophils share common hematopoietic precursors and usually diverge into distinct lineages with unique markers before being released from their hematopoietic site, which is the bone marrow (BM). However, previous studies identified an immature Ly6g(+) Il-5Rα(+) neutrophil population in mouse BM, expressing both neutrophil and eosinophil markers suggesting hematopoietic flexibility. Moreover, others have reported neutrophil populations expressing eosinophil-specific cell surface markers in tissues and altered disease states, confusing the field regarding eosinophil origins, function, and classification. Despite these reports, it is still unclear whether hematopoietic flexibility exists in human granulocytes. To answer this, we utilized single-cell RNA sequencing (scRNA-seq) and CITE-seq to profile human BM and circulating neutrophils and eosinophils at different stages of differentiation and determine whether neutrophil plasticity plays role in asthmatic inflammation. We show that immature metamyelocyte neutrophils in humans expand during severe asthmatic inflammation and express both neutrophil and eosinophil markers. We also show an increase in tri-lobed eosinophils with mixed neutrophil and eosinophil markers in allergic asthma and that IL-5 promotes differentiation of immature blood neutrophils into tri-lobed eosinophilic phenotypes suggesting a mechanism of emergency granulopoiesis to promote myeloid inflammatory or remodeling response in patients with chronic asthma. By providing insights into unexpectedly flexible granulocyte biology and demonstrating emergency hematopoiesis in asthma, our results highlight the importance of granulocyte plasticity in eosinophil development and allergic diseases.

Regiodivergent biosynthesis of bridged bicyclononanes

Medicinal compounds from plants include bicyclo[3.3.1]nonane derivatives, the majority of which are polycyclic polyprenylated acylphloroglucinols (PPAPs). Prototype molecules are hyperforin, the antidepressant constituent of St. John’s wort, and garcinol, a potential anticancer compound. Their complex structures have inspired innovative chemical syntheses, however, their biosynthesis in plants is still enigmatic. PPAPs are divided into two subclasses, named type A and B. Here we identify both types in Hypericum sampsonii plants and isolate two enzymes that regiodivergently convert a common precursor to pivotal type A and B products. Molecular modelling and substrate docking studies reveal inverted substrate binding modes in the two active site cavities. We identify amino acids that stabilize these alternative binding scenarios and use reciprocal mutagenesis to interconvert the enzymatic activities. Our studies elucidate the unique biochemistry that yields type A and B bicyclo[3.3.1]nonane cores in plants, thereby providing key building blocks for biotechnological efforts to sustainably produce these complex compounds for preclinical development.

Properties and Functional Analysis of Two Chorismate Mutases from Maritime Pine.

Through the shikimate pathway, a massive metabolic flux connects the central carbon metabolism with the synthesis of chorismate, the common precursor of the aromatic amino acids phenylalanine, tyrosine, and tryptophan, as well as other compounds, including salicylate or folate. The alternative metabolic channeling of chorismate involves a key branch-point, finely regulated by aromatic amino acid levels. Chorismate mutase catalyzes the conversion of chorismate to prephenate, a precursor of phenylalanine and tyrosine and thus a vast repertoire of fundamental derived compounds, such as flavonoids or lignin. The regulation of this enzyme has been addressed in several plant species, but no study has included conifers or other gymnosperms, despite the importance of the phenolic metabolism for these plants in processes such as lignification and wood formation. Here, we show that maritime pine (Pinus pinaster Aiton) has two genes that encode for chorismate mutase, PpCM1 and PpCM2. Our investigations reveal that these genes encode plastidial isoenzymes displaying activities enhanced by tryptophan and repressed by phenylalanine and tyrosine. Using phylogenetic studies, we have provided new insights into the possible evolutionary origin of the cytosolic chorismate mutases in angiosperms involved in the synthesis of phenylalanine outside the plastid. Studies based on different platforms of gene expression and co-expression analysis have allowed us to propose that PpCM2 plays a central role in the phenylalanine synthesis pathway associated with lignification.

Shared chromosome 21q loss in a mixed subtype renal cell carcinoma: composite or collision tumor?

Clear cell renal cell carcinoma (CCRCC) and papillary renal cell carcinoma (PRCC) are the two most frequentlyencountered subtypes of renal cell carcinoma (RCC). Rarely, these two entities are identified intermingled within thesame mass and have been labeled either collision tumors juxtaposed by random chance or composite tumors thathave arisen from a common tumorigenic precursor cell. Regarding this distinction, authors have commonly reliedupon macroscopic, histologic, and clinicopathologic findings, which may be prone to subjectivity. Objectivemolecular evidence has been lacking. We present a renal tumor showing a mixed CCRCC and PRCC withcorroborating histologic, immunophenotypic, chromosomal microarray analysis (CMA), and next-generationsequencing (NGS) analysis for the respective tumor components, including classic findings of chromosome 3p lossand VHL mutation within the CCRCC component and gain of chromosomes 7 and 17 within the PRCC component.Of novel interest, CMA revealed a shared loss of chromosome 21q in both components with no other identifiableshared or overlapping mutations. This report adds unique evidence supporting the possibility of a true compositerenal cell carcinoma composed of two commonly recognized subtypes. This finding may help to inform earlymolecular pathogenetic mechanism of RCC tumorigenesis.