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The genomes of living lungfishes can inform on the molecular-developmental basis of the Devonian sarcopterygian fish-tetrapod transition. We de novo sequenced the genomes of the African (Protopterus annectens) and South American lungfishes (Lepidosiren paradoxa). The Lepidosiren genome (about 91 Gb, roughly 30 times the human genome) is the largest animal genome sequenced so far and more than twice the size of the Australian (Neoceratodus forsteri)1 and African2 lungfishes owing to enlarged intergenic regions and introns with high repeat content (about 90%). All lungfish genomes continue to expand as some transposable elements (TEs) are still active today. In particular, Lepidosiren's genome grew extremely fast during the past 100 million years (Myr), adding the equivalent of one human genome every 10 Myr. This massive genome expansion seems to be related to a reduction of PIWI-interacting RNAs and C2H2 zinc-finger and Krüppel-associated box (KRAB)-domain protein genes that suppress TE expansions. Although TE abundance facilitates chromosomal rearrangements, lungfish chromosomes still conservatively reflect the ur-tetrapod karyotype. Neoceratodus' limb-like fins still resemble those of their extinct relatives and remained phenotypically static for about 100 Myr. We show that the secondary loss of limb-like appendages in the Lepidosiren-Protopterus ancestor was probably due to loss of sonic hedgehog limb-specific enhancers.

The Mec1/ATR kinase is crucial for genome stability, yet the mechanism by which it prevents gross chromosomal rearrangements (GCRs) remains unknown. Here we find that in cells with deficient Mec1 signaling, GCRs accumulate due to the deregulation of multiple steps in homologous recombination (HR). Mec1 primarily suppresses GCRs through its role in activating the canonical checkpoint kinase Rad53, which ensures the proper control of DNA end resection. Upon loss of Rad53 signaling and resection control, Mec1 becomes hyperactivated and triggers a salvage pathway in which the Sgs1 helicase is recruited to sites of DNA lesions via the 911-Dpb11 scaffolds and phosphorylated by Mec1 to favor heteroduplex rejection and limit HR-driven GCR accumulation. Fusing an ssDNA recognition domain to Sgs1 bypasses the requirement of Mec1 signaling for GCR suppression and nearly eliminates D-loop formation, thus preventing non-allelic recombination events. We propose that Mec1 regulates multiple steps of HR to prevent GCRs while ensuring balanced HR usage when needed for promoting tolerance to replication stress.

ABSTRACT Introduction Methods Results Conclusion Diffuse large B‐cell lymphoma (DLBCL) exhibits striking clinical and biological heterogeneity. Recent studies have identified new subgroups within germinal center B‐cell like (GCB) DLBCL, associated with inferior prognosis, irrespective of MYC and BCL2 translocations. We explored the existence of such a DLBCL high‐risk subgroup, based on multilevel aberrations, especially focusing on MYC and BCL2.Tissue samples from 111 DLBCL patients were sequenced with a 90‐gene lymphoma panel, followed by integrative analyses combining sequencing data, immunohistochemistry, fluorescent in situ hybridization, and clinical data.We identified a high‐risk subgroup in DLBCL defined by: dual immunohistochemical MYC and BCL2 expression (DEL), concurrent MYC and BCL2 translocations (DHL‐BCL2), mutations in MYC, CXCR4, or both, and/or BCL2 amplification. The high‐risk subgroup constituted 41% of the cohort and included DHL‐BCL2, DEL, a GCB subgroup likely representing the recently described GCB subgroups, and a subset of non‐GCB patients. In multivariate analysis, high‐risk features provided independent predictive value from age and IPI. The 5‐year overall survival was 36% in high‐risk patients, compared to 76% in non‐high‐risk patients.We identified a distinct high‐risk DLBCL subgroup, characterized by MYC and BCL2 aberrations, beyond conventional DHL‐BCL2 and DEL, and irrespective of cell‐of‐origin, thereby expanding the poor‐prognosis group. [ABSTRACT FROM AUTHOR]

Quantifying the features of mitochondrial genome structural variation is crucial for understanding its contribution to complexity. Accurate quantification and interpretation of organizational diversity can help uncover biological evolutionary laws and patterns. The current qMGR approach accumulates the changes in two adjacent genes to calculate the rearrangement frequency RF of each single gene and the rearrangement score RS for specific taxa in the mitogenomes of a given taxonomic group. However, it may introduce bias, as it assigns scores to adjacent genes rather than to rearranged genes. To overcome this limitation, we propose a novel statistical method called qGO to quantify the diversity of gene organization. The qGO method, which is based on the homology of gene order, provides a more accurate representation of genome organizational diversity by partitioning gene strings and individually assigning weights to genes spanning different regions. Additionally, a comprehensive approach is employed for distance computation, generating an extensive matrix of rearrangement distances. Through experiments on more than 5500 vertebrate mitochondrial genomes, we demonstrated that the qGO method outperforms existing methods in terms of accuracy and interpretability. This method improves the comparability of genomes and allows a more accurate comparison of the diversity of mitochondrial genome organization across taxa. These findings have significant implications for unraveling genome evolution, exploring genome function, and investigating the process of molecular evolution. [ABSTRACT FROM AUTHOR]

Complex structural variations (cxSVs) are often overlooked in genome analyses due to detection challenges. We developed ARC-SV, a probabilistic and machine-learning-based method that enables accurate detection and reconstruction of cxSVs from standard datasets. By applying ARC-SV across 4,262 genomes representing all continental populations, we identified cxSVs as a significant source of natural human genetic variation. Rare cxSVs have a propensity to occur in neural genes and loci that underwent rapid human-specific evolution, including those regulating corticogenesis. By performing single-nucleus multiomics in postmortem brains, we discovered cxSVs associated with differential gene expression and chromatin accessibility across various brain regions and cell types. Additionally, cxSVs detected in brains of psychiatric cases are enriched for linkage with psychiatric GWAS risk alleles detected in the same brains. Furthermore, our analysis revealed significantly decreased brain-region- and cell-type-specific expression of cxSV genes, specifically for psychiatric cases, implicating cxSVs in the molecular etiology of major neuropsychiatric disorders. [Display omitted] • ARC-SV uses machine learning on pangenomes to detect cxSVs with high accuracy • Rare cxSVs in the human population are enriched in neural genes • Rare cxSVs are enriched in loci that underwent rapid human-specific evolution • cxSVs contribute to the genetic architecture of major psychiatric disorders ARC-SV enables highly accurate detection and characterization of localized complex rearrangements of multiple DNA segments. Applying ARC-SV across human populations and brain cohorts uncovers connections between complex structural variantion and human-specific evolution, neural genes, and major psychiatric disorders. [ABSTRACT FROM AUTHOR]

AbstractZNF384 gene rearrangements are a distinct subtype of adult B cell acute lymphoblastic leukemia (B-ALL). We screened 46 B-other ALL patients for ZNF384 fusions using fluorescent in situ hybridization (FISH) and reverse transcription-polymerase chain reaction (RT-PCR). Clinical data, treatment response, and minimal residual disease (MRD) status were analyzed. Ten (21.7%) patients were ZNF384-r positive (nine by FISH, nine by RT-PCR, eight by both). FISH showed atypical signals, including 3’ signal gain and 5’ signal deletion. EP300 was the main fusion partner (n = 5). TAF15::ZNF384, SYNRG::ZNF384, CREBBP::ZNF384, and TCF3::ZNF384 fusions were found in one patient each; one case’s partner gene is unknown. One patient was MRD-negative at the end of the first induction, lower than in patients without ZNF384-r. ZNF384-r incidence matched B-other ALL incidence in Chinese patients. Combined FISH and RT-PCR improved detection. ALL with ZNF384-r has unique features, and lower MRD-negative response may indicate a negative impact on traditional treatments. [ABSTRACT FROM AUTHOR]

Background: Lottiidae (Gray, 1840) is a derived family of Patellogastropoda and an important component of intertidal benthic communities. The mitochondrial genome (mitogenome) has been frequently used to analyze the phylogenetic relationships of Patellogastropoda. We used next-generation sequencing (NGS) to sequence the complete mitogenomes of five species. We analyzed the basic base composition characteristics of these mitogenomes, constructed a phylogenetic tree, compared the characteristics of gene rearrangement with other related species, and discussed the evolutionary patterns between gastropod species and the evolutionary relationships of each subclass. In addition, we aim to infer the differentiation time and evolutionary characteristics of various species in the order Patellogastropoda. These results will enrich the mitogenome database of Patellogastropoda and enhance our understanding of the genetic characteristics of Lottiidae and the phylogenetic relationships between gastropods. Results: We obtained the mitogenomes sequences of Lottia peitaihoensis, Patelloida saccharinoides, Patelloida ryukyuensis, Nipponacmea sp. and Nipponacmea nigrans, using next-generation sequencing technology. We analyzed the basic structural characteristics of their mitogenomes and found that their lengths ranged from 16.6 kbp to 19.1 kbp. While N. nigrans and P. saccharinoides contain 39 genes, L. peitaihoensis, P. ryukyuensis, and Nipponacmea sp. have only 38 genes, with one trnW less. The most abundant base among the five species is T, and most protein coding genes (PCGs) use ATT, ATG, and ATA as starting codons, and TAA and TAG as stopping codons. We selected the mitogenomes of 10 Lottiidae species for selection pressure analysis and found that all PCGs were subject to purifying selection. Phylogenetic analysis indicates that Patellogastropoda is a fundamental branch of the Gastropoda, and Lottiidae, within Patellogastropoda, is an independent branch at the outermost of the entire phylogenetic tree. Comparison of mitochondrial gene sequences of all Patellogastropoda species revealed a high degree of gene rearrangement within the family Lottiidae, eight sequences present among the 10 species examined. By estimating their divergence times, we found that the divergence of limpets occurred as early as the Permian period of the Paleozoic Era, and a large number of species diverged in the Cenozoic Era. Conclusion: The data obtained from this study will provide information on the assembly of the mitochondrial genome of the Lottiidae species, which will contribute to a better understanding of the evolutionary status and relationship among thes family of Patellogastropoda. [ABSTRACT FROM AUTHOR]

Background Method Results Conclusions Mitochondrial DNA (mtDNA) rearrangements are recognised factors in mitochondrial disorders and ageing, but their involvement in neurodevelopmental disorders, particularly intellectual disability (ID) and autism spectrum disorder (ASD), remains poorly understood. Previous studies have reported mitochondrial dysfunction in individuals with both ID and ASD. The aim of this study was to investigate the prevalence of large‐scale mtDNA rearrangements in ID and ID with comorbid ASD (ID‐ASD).We used mtDNA‐targeted next‐generation sequencing and the MitoSAlt high‐throughput computational pipeline in peripheral blood samples from 76 patients with ID (mean age 52.5 years, 37% female), 59 patients with ID‐ASD (mean age 41.3 years, 46% female) and 32 healthy controls (mean age 42.4 years, 47% female) from Catalonia.The study revealed a high frequency of mtDNA rearrangements in patients with ID, with 10/76 (13.2%) affected individuals. However, the prevalence was significantly lower in patients with ID‐ASD 1/59 (1.7%) and in HC 1/32 (3.1%). Among the mtDNA rearrangements, six were identified as deletions (median size 6937 bp and median heteroplasmy level 2.3%) and six as duplications (median size 10 455 bp and median heteroplasmy level 1.9%). One of the duplications, MT‐ATP6 m.8765‐8793dup (29 bp), was present in four individuals with ID with a median heteroplasmy level of 3.9%.Our results show that mtDNA rearrangements are frequent in patients with ID, but not in those with ID‐ASD, when compared to HC. Additionally, MitoSAlt has demonstrated high sensitivity and accuracy in detecting mtDNA rearrangements, even at very low heteroplasmy levels in blood samples. While the high frequency of mtDNA rearrangements in ID is noteworthy, the role of these rearrangements is currently unclear and needs to be confirmed with further data, particularly in post‐mitotic tissues and through age‐matched control studies. [ABSTRACT FROM AUTHOR]

Genomic instability is a core characteristic of cancer, often stemming from defects in DNA damage response (DDR) or increased replication stress. DDR defects can lead to significant genetic alterations, including changes in gene copy numbers, gene rearrangements, and mutations, which accumulate over time and drive the clonal evolution of cancer cells. However, these vulnerabilities also present opportunities for targeted therapies that exploit DDR deficiencies, potentially improving treatment efficacy and patient outcomes. The development of PARP inhibitors like Olaparib has significantly improved the treatment of cancers with DDR defects (e.g., BRCA1 or BRCA2 mutations) based on synthetic lethality. This achievement has spurred further research into identifying additional therapeutic targets within the DDR pathway. Recent progress includes the development of inhibitors targeting other key DDR components such as DNA-PK, ATM, ATR, Chk1, Chk2, and Wee1 kinases. Current research is focused on optimizing these therapies by developing predictive biomarkers for treatment response, analyzing mechanisms of resistance (both intrinsic and acquired), and exploring the potential for combining DDR-targeted therapies with chemotherapy, radiotherapy, and immunotherapy. This article provides an overview of the latest advancements in targeted anti-tumor therapies based on DDR and their implications for future cancer treatment strategies. [ABSTRACT FROM AUTHOR]

Multiple pathways are known to suppress the formation of gross chromosomal rearrangements (GCRs), which can cause human diseases including cancer. In contrast, much less is known about pathways that promote their formation. The spindle assembly checkpoint (SAC), which ensures the proper separation of chromosomes during mitosis, has been reported to promote GCR, possibly by delaying mitosis to allow GCR-inducing DNA repair to occur. Here, we show that this conclusion is the result of an experimental artifact arising from the synthetic lethality caused by the disruption of the SAC and loss of the CIN8 gene, which is often lost in the genetic assay used to select for GCRs. After correcting for this artifact, we find no role of the SAC in promoting GCR. [ABSTRACT FROM AUTHOR]

Context.--: Perivascular epithelioid cell tumors (PEComas) are rare mesenchymal tumors of uncertain histogenesis expressing smooth muscle and melanocytic markers. The clinicopathologic spectrum in young patients is not well documented. Objective.--: To describe a multi-institutional series of PEComas in children, adolescents, and young adults. Design.--: PEComas, not otherwise specified (NOS); angiomyolipomas (AMLs); lymphangioleiomyomatosis; and clear cell sugar tumors were retrospectively identified from 6 institutions and the authors' files. Results.--: Seventy PEComas in 64 patients (median age, 15 years) were identified. They were more common in females (45 of 64 patients), occurring predominantly in the kidney (53 of 70), followed by the liver (6 of 70). Thirty-four patients had confirmed tuberous sclerosis complex (TSC), 3 suspected TSC mosaicism, 2 Li-Fraumeni syndrome (LFS) and 1 neurofibromatosis type 1. Most common variants were classic (49 of 70) and epithelioid (8 of 70) AML. Among patients with AMLs, most (34 of 47) had TSC, and more TSC patients had multiple AMLs (15 of 36) than non-TSC patients (2 of 13). Two TSC patients developed malignant transformation of classic AMLs: 1 angiosarcomatous and 1 malignant epithelioid. Lymphangioleiomyomatosis (5 of 70) occurred in females only, usually in the TSC context (4 of 5). PEComas-NOS (6 of 70) occurred exclusively in non-TSC patients, 2 of whom had LFS (2 of 6). Three were malignant, 1 had uncertain malignant potential, and 2 were benign. All 4 PEComas-NOS in non-LFS patients had TFE3 rearrangements. Conclusions.--: Compared to the general population, TSC was more prevalent in our cohort; PEComas-NOS showed more frequent TFE3 rearrangements and possible association with LFS. This series expands the spectrum of PEComas in young patients and demonstrates molecular features and germline contexts that set them apart from older patients. [ABSTRACT FROM AUTHOR]

Until the early 2000s, advanced or metastatic non–small cell lung cancer (NSCLC) was treated as a single disease with all histologic subtypes treated alike with standard chemotherapy agents. Over the past two decades, the treatment paradigms for advanced NSCLC have changed dramatically with the discovery of multiple targeted therapies that are now approved for the treatment of NSCLC tumors with specific oncogene drivers or molecular alterations. Molecular testing has become integrated and critical for the clinical management of advanced NSCLC. The discovery and success of these targeted therapies have reshaped the classification of NSCLC on the basis of molecular classification and enabled a personalized approach in thoracic oncology. In this review, we discuss recent developments in the molecular profiling of NSCLC, and approved and emerging targeted therapies for the treatment of NSCLC. In this review, we discuss recent developments in the molecular profiling of non–small cell lung cancer (NSCLC), and approved and emerging targeted therapies for the treatment of NSCLC. [ABSTRACT FROM AUTHOR]

The quality of Recombination signal sequences (RSSs), location, and genetics of mammalian V, D, and J genes synergistically affect the recombination frequency of genes; however, the specific regulatory mechanism and efficiency have not been elucidated. By taking advantage of single-cell RNA-sequencing (scRNA-seq) and high-throughput sequencing (HTS) to investigate V(D)J rearrangement characteristics in the CDR3 repertoire, we found that the distal and proximal V genes (or J genes) "to D" gene were involved in rearrangement significantly more frequently than the middle V genes (or J genes) in the TRB locus among various species, including Primates (human and rhesus monkey), Rodentia (BALB/c, C57BL/6, and Kunming mice), Artiodactyla (buffalo), and Chiroptera (Rhinolophus affinis). The RSS quality of the V and J genes affected their frequency in rearrangement to varying degrees, especially when the V-RSSs with recombination signal information content (RIC) score < -45 significantly reduced the recombination frequency of the V gene. The V and J genes that were "away from D" had the dual advantages of recombinant structural accessibility and relatively high-quality RSSs, which promoted their preferential utilization in rearrangement. The quality of J-RSSs formed during mammalian evolution was apparently greater than that of V-RSSs, and the D-J distance was obviously shorter than that of V-D, which may be one of the reasons for guaranteeing that the "D-to-J preceding V-to-DJ rule" occurred when rearranged. This study provides a novel perspective on the mechanism and efficiency of V-D-J rearrangement in the mammalian TRB locus, as well as the biased utilization characteristics and application of V and J genes in the initial CDR3 repertoire. Significance: HTS and scRNA-seq were used to sequence the TCRβ CDR3 repertoire of human, rhesus monkey, mouse, bat, and buffalo (central and peripheral tissue samples), revealing non-randomness and non-heterogeneity in the frequency of V and J genes usage, with a consistent trend of biased rearrangement among different mammalian V and J genes. It was first discovered in the TCRβ CDR3 repertoire of Primate (human and rhesus monkey), Rodentia (BALB/c, C57BL/6, and Kunming mice), Artiodactyla (buffalo), and Chiroptera (Rhinolophus affinis) in mammals: relative to the location of the D gene in the TRB locus, the recombination frequency of the distal and proximal V genes (or J genes) "to D" gene was obviously higher than that of the middle V genes (or J genes); the RSS quality of V and J genes had important consequences with the participation of V and J genes in rearrangement, especially when V RIC scores < − 45, the efficiency of rearrangement was significantly decreased; in mammalian evolution, the J-RSSs demonstrated a superior level of quality compared with the V-RSSs, and there was a noticeable reduction in the D-J distance compared with the V-D, which determined the order (sequential) and efficiency (bias) of V and J genes involved in rearrangement. [ABSTRACT FROM AUTHOR]

Background: Solitary fibroous tumors (SFTs) are distinctive soft tissue tumors characterized by rearrangements of NAB2-STAT6 gene, which are associated with thin-walled, branching, "staghorn"-shaped vessels. SFTs are originally classified as a type of hemangiopericytoma (HPC). Classical SFTs are composed of spindle to ovoid cells arranged haphazardly or in fascicles. Rarely, SFTs exhibit unusual morphological variants such as fat formation, giant cells, dedifferentiation, or epithelioid variant. The epithelioid cell variant, which is composed almost entirely of epithelioid cells and arranged in solid or nest patterns, is extremely rare and frequently malignant. Case presentation: In this study, we reported three cases of epithelioid SFTs (ESFTs) located in extrathoracic sites (right lateral ventricle, right lumbar, left pelvis). All the subjects in this study were elderly, with a predominance of female patients, accounting for two out of the three cases, and only one case involved a male patient. The tumor cells were entirely composed of epithelioid cells and exhibited positive for CD34 and STAT-6 markers. Ultimately, the majority of cases (two out of three) were diagnosed as malignant SFTs. Conclusion: This study aims to enhance the awareness of ESFTs. In these cases, irrespective of the onset location, the arrangement patterns of tumor cells, such as papillary structures and the morphology of epithelial-like cells, conspicuously lack the hallmark histological characteristics of Solitary Fibrous Tumors (SFTs). Consequently, it requires differential diagnosis from a plethora of malignant neoplasms. Moreover, the elevated malignancy level of this cohort of cases poses substantial diagnostic challenges to pathologists, compounding the complexity of accurate interpretation. [ABSTRACT FROM AUTHOR]

Differentiated thyroid cancers (DTCs) constitute the primary histological subtype within thyroid cancer. Due to DTCs distinctive radioiodine (RAI) uptake mechanism, standard treatment involving surgery, with or without adjunctive therapy using RAI and levothyroxine inhibition, typically yields favorable prognoses for the majority of patients with DTCs. However, this favorable outcome does not extend to individuals with decreased RAI uptake, termed radioiodine-refractory thyroid cancers (RAI-RTCs). Recent research has revealed that the genetic mutations and gene rearrangements affecting sites such as RTKs, RAS, BRAF and TERTp lead to structural and functional abnormalities in encoded proteins. These abnormalities aberrantly activate signaling pathways like the mitogen-activated protein kinase (MAPK) and phosphatidylinositol-3-hydroxykinase (PI3K) signaling pathways, resulting in thyroid cells dedifferentiation, sodium/iodide symporter (NIS) dysfunction, and consequent the RAI-refractory nature of DTCs. Targeted therapy tailored to mutations presents a promising avenue for the treatment of RAI-RTCs. Lenvatinib and sorafenib, multi-kinase inhibitors, represent the standard first-line systemic treatment options, while cabozantinib is the standard second-line treatment option, for this purpose. Furthermore, ongoing clinical trials are exploring selective kinase inhibitors, immune checkpoint inhibitors, and combination therapies. Notably, numerous clinical trials have demonstrated that selective kinase inhibitors like BRAF, MEK and mTOR inhibitors can restore RAI uptake in tumor cells. However, further validation through multicenter, large-sample, double-blinded randomized controlled trials are essential. Enhanced treatment strategies and innovative therapies are expected to benefit a broader spectrum of patients as these advancements progress. [ABSTRACT FROM AUTHOR]

The article discusses the use of next-generation sequencing and high DNA input to detect measurable residual disease (MRD) in the peripheral blood of patients with B-cell precursor acute lymphoblastic leukemia (ALL). Traditional MRD assessment in bone marrow samples may miss MRD in peripheral blood, but modern molecular methods can enhance detection. The study found that adjusting traditional MRD assessment strategies can improve MRD detection in peripheral blood, but it may not fully replace bone marrow monitoring. The findings suggest that high DNA input and next-generation sequencing can increase the sensitivity of MRD detection in peripheral blood, especially in cases where bone marrow samples are unavailable. [Extracted from the article]

This study presents the first genome and transcriptome analyses for Fusarium oxysporum f. sp. lactucae (Fola) which causes Fusarium wilt disease of lettuce. Long-read genome sequencing of three race 1 (Fola1) and three race 4 (Fola4) isolates revealed key differences in putative effector complement between races and with other F. oxysporum ff. spp. following mimp-based bioinformatic analyses. Notably, homologues of Secreted in Xylem (SIX) genes, also present in many other F. oxysporum ff. spp, were identified in Fola, with both SIX9 and SIX14 (multiple copies with sequence variants) present in both Fola1 and Fola4. All Fola4 isolates also contained an additional single copy of SIX8. RNAseq of lettuce following infection with Fola1 and Fola4 isolates identified highly expressed effectors, some of which were homologues of those reported in other F. oxysporum ff. spp. including several in F. oxysporum f. sp. apii. Although SIX8, SIX9 and SIX14 were all highly expressed in Fola4, of the two SIX genes present in Fola1, only SIX9 was expressed as further analysis revealed that SIX14 gene copies were disrupted by insertion of a transposable element. Two variants of Fola4 were also identified based on different genome and effector-based analyses. This included two different SIX8 sequence variants which were divergently transcribed from a shared promoter with either PSE1 or PSL1 respectively. In addition, there was evidence of two independent instances of HCT in the different Fola4 variants. The involvement of helitrons in Fola genome rearrangement and gene expression is discussed. [ABSTRACT FROM AUTHOR]

AbstractThe complete mitochondrial genomes of octocorals typically range from 18.5 kb to 20.5 kb in length and include 14 protein-coding genes (PCGs), two ribosomal RNA genes and one tRNA. To date, seven different gene orders (A–G) have been described, yet comprehensive investigations of the actual number of arrangements, as well as comparative analyses and evolutionary reconstructions of mitochondrial genome evolution within the whole class Octocorallia, have been often overlooked. Here, we considered the complete mitochondrial genomes available for octocorals and explored their structure and gene order variability. Our results updated the actual number of mitochondrial gene order arrangements so far known for octocorals from 7 to 14 and allowed us to explore and preliminarily discuss the role of some of the structural and functional factors in the mitogenomes. We performed comparative mitogenomic analyses on the existing and novel octocoral gene orders, considering different mitogenomic structural features such as genome size, GC percentage, AT and GC skewness. The mitochondrial gene order history mapped on a recently published nuclear loci phylogeny showed that the most common rearrangement events in octocorals are inversions, inverted transpositions and transpositions. Furthermore, gene order rearrangement events were restricted only to some regions of the tree. Overall, different rearrangement events arose independently and from the ancestral and most common gene order, instead of being derived from other rearranged orders. Finally, our data demonstrate how the study of mitochondrial gene orders can be used to explore the evolution of octocorals and in some cases can be used to assess the phylogenetic placement of certain taxa. [ABSTRACT FROM AUTHOR]

SUMMARY: DNA rearrangements, including inversions, translocations, and large insertions/deletions (indels), are crucial for crop evolution, domestication, and improvement. The rearrangements are frequently induced by ion beams via the mis‐repair of DNA double‐strand breaks (DSBs). Unfortunately, how ion beam‐induced DSBs are repaired has not been comprehensively analyzed and the mechanisms underlying DNA rearrangements remain unclear. In this study, clonal sectors originating from single mutated cells in carbon ion‐irradiated plants were used for whole‐genome sequencing analyses after Arabidopsis seeds and seedlings were irradiated. Comparative analyses of the induced mutations (e.g., size and frequency of indels and microhomology at the junctions of the rearrangements) in the irradiated materials suggested that the broken/rejoined DSB ends were more extensively processed in seedlings than in seeds. A mutation to canonical non‐homologous end‐joining (c‐NHEJ), which is a DSB repair pathway with minimal processing of DSB ends, increased the sensitivity to ion beams more in the seeds than in the seedlings, which was consistent with the junction analysis results, indicative of the minor contribution of c‐NHEJ to the carbon ion‐induced DSB repair in seedlings. Considering the characteristics of the large templated insertions in irradiated seedlings, ion‐beam‐induced DSBs in seedlings are likely repaired primarily by a polymerase theta‐mediated pathway. Polymerase theta‐deficient seedlings were more sensitive to ion beams than the c‐NHEJ‐deficient seedlings, consistent with this hypothesis. This study revealed the key characteristics of ion beam‐induced DSBs and the associated repair mechanisms related to the physiological status of the irradiated materials, with implications for elucidating the occurrence and induction of rearrangements. Significance Statement: DNA rearrangements, which are critical for crop improvement, can be randomly induced in genomes by ion beams. Our genomic analysis of irradiated plants revealed significant differences in the characteristics of the DNA rearrangements in seeds and seedlings, providing important insights into double‐strand break repair mechanisms and the associated rearrangement formation related to the physiological status of the irradiated materials. [ABSTRACT FROM AUTHOR]

Background: The Caridea, affiliated with Malacostraca, Decapoda, and Pleocyemata, constitute one of the most significant shrimp groups. They are widely distributed across diverse aquatic habitats worldwide, enriching their evolutionary history. In recent years, considerable attention has been focused on the classification and systematic evolution of Caridea, yet controversies still exist regarding the phylogenetic relationships among families. Methods: Here, the complete mitochondrial genome (mitogenome) sequences of five caridean species, namely Heterocarpus sibogae, Procletes levicarina, Macrobrachium sp., Latreutes anoplonyx, and Atya gabonensis, were determined using second-generation high-throughput sequencing technology. The basic structural characteristics, nucleotide composition, amino acid content, and codon usage bias of their mitogenomes were analyzed. Selection pressure values of protein-coding genes (PCGs) in species within the families Pandalidae, Palaemonidae, and Atyidae were also computed. Phylogenetic trees based on the nucleotide and amino acid sequences of 13 PCGs from 103 caridean species were constructed, and divergence times for various families within Caridea were estimated. Results: The mitogenome of these five caridean species vary in length from 15,782 to 16,420 base pairs, encoding a total of 37 or 38 genes, including 13 PCGs, 2 rRNA genes, and 22 or 23 tRNA genes. Specifically, L. anoplonyx encodes an additional tRNA gene, bringing its total gene count to 38. The base composition of the mitogenomes of these five species exhibited a higher proportion of adenine-thymine (AT) bases. Six start codons and four stop codons were identified across the five species. Analysis of amino acid content and codon usage revealed variations among the five species. Analysis of selective pressure in Pandalidae, Palaemonidae, and Atyidae showed that the Ka/Ks values of PCGs in all three families were less than 1, indicating that purifying selection is influencing on their evolution. Phylogenetic analysis revealed that each family within Caridea is monophyletic. The results of gene rearrangement and phylogenetic analysis demonstrated correlations between these two aspects. Divergence time estimation, supported by fossil records, indicated that the divergence of Caridea species occurred in the Triassic period of the Mesozoic era, with subsequent differentiation into two major lineages during the Jurassic period. Conclusions: This study explored the fundamental characteristics and phylogenetic relationships of mitogenomes within the infraorder Caridea, providing valuable insights into their classification, interspecific evolutionary patterns, and the evolutionary status of various Caridea families. The findings provide essential references for identifying shrimp species and detecting significant gene rearrangements within the Caridea infraorder. [ABSTRACT FROM AUTHOR]

Genomic instability is a core characteristic of cancer, often stemming from defects in DNA damage response (DDR) or increased replication stress. DDR defects can lead to significant genetic alterations, including changes in gene copy numbers, gene rearrangements, and mutations, which accumulate over time and drive the clonal evolution of cancer cells. However, these vulnerabilities also present opportunities for targeted therapies that exploit DDR deficiencies, potentially improving treatment efficacy and patient outcomes. The development of PARP inhibitors like Olaparib has significantly improved the treatment of cancers with DDR defects (e.g., BRCA1 or BRCA2 mutations) based on synthetic lethality. This achievement has spurred further research into identifying additional therapeutic targets within the DDR pathway. Recent progress includes the development of inhibitors targeting other key DDR components such as DNA-PK, ATM, ATR, Chk1, Chk2, and Wee1 kinases. Current research is focused on optimizing these therapies by developing predictive biomarkers for treatment response, analyzing mechanisms of resistance (both intrinsic and acquired), and exploring the potential for combining DDR-targeted therapies with chemotherapy, radiotherapy, and immunotherapy. This article provides an overview of the latest advancements in targeted anti-tumor therapies based on DDR and their implications for future cancer treatment strategies. [ABSTRACT FROM AUTHOR]

Pleurogenoides japonicus (Trematoda: Microphalloidea) is an important parasite in wood frogs with high infection rates and significant ecological, economic, and societal importance. The scarcity of molecular data for these parasites severely limits population genetics and phylogenetic studies. In the present study, for the first time, we determined and described the entire mitochondrial (mt) genome of P. japonicus as the first representative of the family Pleurogenidae. The entire mt genome of P. japonicus was circular, with 15,043 bp (GenBank accession number OR900118), containing 36 genes, comprising 12 protein‐coding genes (cox1–3, nad1–6, nad4L, cytb, and atp6), two ribosomal RNA genes, 22 transfer RNA genes, and two non‐coding regions. There were 23 intergenic spacers, ranging from 2 to 162 bp, and only one 40 bp overlap between nad4L and nad4 genes in the P. japonicus mt genome. The nucleotide composition of P. japonicus mt genome exhibited a strong AT bias with a 63.75% A + T content, while the AT‐ and GC‐skews were − 0.435 and 0.407, respectively. Comparative analysis demonstrated that the P. japonicus mt genome shared the most common characteristics with Microphalloidea trematodes, and the cox1 gene was the longest and most conserved gene in Microphalloidea trematodes. The gene arrangements of Xiphidiata trematodes were of the same order based on protein‐coding genes and rRNA genes, except for tRNA. More than two gene arrangement types exist in Echinostomata and Xiphidiata, and the gene rearrangement events mainly occurred in "trnE‐trnG" and "trnG‐trnE". Phylogenetic analysis suggested that trematodes of the family Pleurogenidae clustered more with Prosthogonimidae than Eucotylidae. The mt genome data of P. japonicus provide an accurate genetic marker for further studies of Xiphidiata trematodes. [ABSTRACT FROM AUTHOR]

Simple Summary: Little is known about the molecular data and phylogenetic relationships of scoliid wasps. In this study, we determined 10 mitochondrial genomes representing eight genera in two tribes of the family Scoliidae distributed in China, compared and analyzed all Chinese genus representatives for general features and rearrangement. Phylogenetic relationships between them were inferred using MrBayes and IQtree based on four data matrices. Gene rearrangement was chosen for ancestral state reconstruction. Our results support most of the relationships between genera and tribes of Scoliidae in former morphological studies except for the Colpa group, which is proved to be closer to Scoliini based on our genome features, phylogenetic analyses and some morphological evidence. Scoliidae, also known as scarab hunters or flower wasps, are important in the biological control of scarabs and for pollination. Mitogenomic and phylogenetic studies are rare for this group. In this study, 10 mitochondrial genomes representing eight genera in two tribes of the family Scoliidae were determined. The general features and rearrangements of the mitochondrial genomes for 15 Scoliidae species representing all genera distributed in China were described and compared and the phylogenetic relationships among them were inferred using MrBayes and IQtree based on four data matrices. Most sequences of Scoliidae have one extra trnM gene. Species belonging to Campsomerini have lower A + T content than all Scoliini species except for Colpa tartara in this study. The AT-skew is positive in 7 out of 15 species. All 15 Scoliidae sequences have similar conserved gene arrangements with the same arrangements of PCGs and rRNA genes, except for Campsomeriella annulata. The tRNA genes have the highest frequency of rearrangement, and C. tartara is always rearranged as in its Scoliini counterparts. Our phylogenetic results support most of the relationships between genera and tribes of Scoliidae in former morphological studies. However, Colpa tartara is proved to be closer to Scoliini according to genome features, phylogenetic analyses and some morphological evidence, which challenges the former attribution of the Colpa group. [ABSTRACT FROM AUTHOR]

Tumor cells of acute lymphoblastic leukemia (ALL) may have various genetic abnormalities. Some of them lead to a complete loss of certain genes. Our aim was to reveal biallelic deletions of genes in Ph–negative T-ALL. Chromosomal microarray analysis (CMA) was performed for 47 patients with de novo Ph–negative T-ALL, who received treatment according to RALL-2016m clinical protocol at the National Medical Research Center for Hematology (Moscow, Russia) from 2017 to 2023. Out of forty-seven patients, only three had normal molecular karyotype. The other 44 patients had multiple gains, losses, and copy neutral losses of heterozygosity. Biallelic losses were found in 14 patients (30%). In ten patients (21%), a biallelic deletion of 9p21.3 involved a different number of genes, however CDKN2A gene loss was noted in all ten cases. For seven patients (15%), a biallelic deletion of 7q34 was found, including two genes—PRSS1, PRSS2 located within the T-cell receptor beta (TRB) locus. A clonal rearrangement of the TRB gene was revealed in 6 out of 7 cases with 7q34 biallelic loss. Both biallelic deletions can be considered favorable prognostic factors, with an association with 9p21 being statistically significant (p = 0.01) and a trend for 7q34 (p = 0.12) being observed. [ABSTRACT FROM AUTHOR]

Sugarcane thrips, Fulmekiola serrata (Kobus) (Thysanoptera: Thripidae), is a common foliar pest that infests sugarcane and is found throughout tropical and subtropical countries. In this study, we obtained and analyzed the complete mitochondrial genome of F. serrata for the first time and explored the phylogenetic relationships of the higher-order elements of Thysanoptera members at the mitochondrial level. The complete mitochondrial genome of F. serrata is 16,596 bp in length and includes 13 protein-coding genes (PCGs), 22 transfer RNA (tRNA) genes, 2 ribosomal RNA (rRNA) genes, and 1 noncoding control region. A+T accounted for 75% of the total bases in the mitochondrial genome of F. serrata, revealing an obvious AT bias. Among the 13 PCGs, except for nad5, which had a start codon of TTG, the remaining genes had ATNs typical of insects (ATA, ATT, ATC, and ATG); nad1, nad2, nad3, and atp8 had incomplete termination codons of TA or T. The remaining nine PCGs were complete with the termination codon TAA. Of the 22 tRNA secondary structures, all were typical cloverleaf secondary structures except for trnS1, which was missing the DHU arm. Compared with the hypothetical ancestral gene arrangement of arthropods, F. serrata presented extensive gene rearrangement, with 23 translocated genes, 8 inverted genes, and 5 shuffled genes. Both maximum likelihood (ML) and Bayesian inference (BI) phylogenetic trees resulted in similar topologies: ((Thripidae + (Stenurothripidae + Aeolothripidae)) + Phlaeothripidae), with Thripidae, Aeolothripidae and Phlaeothripidae being monophyletic groups, whereas F. serrata is closely related to Thrips palmi, and the two are sister groups. [ABSTRACT FROM AUTHOR]

The Doradidae fishes constitute one of the most diverse groups of Neotropical freshwater environments. Acanthodoradinae is the oldest lineage and the sister group to all other thorny catfishes, and it includes only the genus Acanthodoras. The diversity of Acanthodoras remains underestimated, and the use of complementary approaches, including genetic studies, is an important step to better characterize this diversity and the relationships among the species within the genus. Therefore, we conducted a comprehensive analysis using conventional cytogenetic techniques and physical mapping of three multigene families (18S and 5S ribosomal DNA [rDNA], U2 small nuclear DNA [snDNA]) and four microsatellite motifs, namely (AC)n, (AT)n, (GA)n, and (GATA)n, in two sympatric species from the Negro River: Acanthodoras cataphractus and Acanthodoras cf. polygrammus. We found significant differences in constitutive heterochromatin (CH) content, distribution of the microsatellite (AT)n, and the number of 5S rDNA and U2 snDNA sites. These differences may result from chromosome rearrangements and repetitive DNA dispersal mechanisms. Furthermore, the characterization of the diploid number (2n) of these Acanthodoras species enables us to propose 2n = 58 chromosomes as the plesiomorphic 2n state in Doradidae based on ancestral state reconstruction. Acanthodoradinae is the oldest lineage of the thorny catfishes, and knowledge about its cytogenetic patterns is crucial for disentangling the karyotype evolution of the whole group. Thus, this study contributes to the understanding of the mechanisms behind chromosome diversification of Doradidae and highlights the importance of Acanthodoradinae in the evolutionary history of thorny catfishes. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the possibility of distinguishing between IgG4-related ophthalmic disease (IgG4-ROD) and orbital MALT lymphoma using artificial intelligence (AI) and hematoxylin–eosin (HE) images. Methods: After identifying a total of 127 patients from whom we were able to procure tissue blocks with IgG4-ROD and orbital MALT lymphoma, we performed histological and molecular genetic analyses, such as gene rearrangement. Subsequently, pathological HE images were collected from these patients followed by the cutting out of 10 different image patches from the HE image of each patient. A total of 970 image patches from the 97 patients were used to construct nine different models of deep learning, and the 300 image patches from the remaining 30 patients were used to evaluate the diagnostic performance of the models. Area under the curve (AUC) and accuracy (ACC) were used for the performance evaluation of the deep learning models. In addition, four ophthalmologists performed the binary classification between IgG4-ROD and orbital MALT lymphoma. Results: EVA, which is a vision-centric foundation model to explore the limits of visual representation, was the best deep learning model among the nine models. The results of EVA were ACC = 73.3% and AUC = 0.807. The ACC of the four ophthalmologists ranged from 40 to 60%. Conclusions: It was possible to construct an AI software based on deep learning that was able to distinguish between IgG4-ROD and orbital MALT. This AI model may be useful as an initial screening tool to direct further ancillary investigations. [ABSTRACT FROM AUTHOR]

Objective: the study aimed to characterize the novel entity referred to as secretory carcinoma of the salivary glands. Methods: we comprehensively evaluated 150 patients afflicted by malignant salivary gland tumors who had been under treatment at the University of Verona. Inclusion criteria primarily focused on the availability of paraffin block materials and adequate follow-up data. Subsequently, we conducted a comprehensive Fluorescent In Situ Hybridization (FISH) analysis, utilizing probes targeting NTRK-3, MALM-2, EWRS-1, HER-2, MDM-2, and NTRK1-2. Results: out of the initial cohort, 37 patients met the eligibility criteria for our study. We identified NTRK3 gene rearrangements in four patients (11%), two of whom had mucoepidermoid carcinoma, and the remaining two had acinic cell carcinoma. Notably, none of these patients had initially received a secretory carcinoma diagnosis. The primary treatment approach for all patients entailed surgical parotid gland resection. The overall survival (OS) for patients with NTRK3 rearrangements amounted to 78 months, with a corresponding progression-free survival (PFS) of 73 months. Conclusion: in summary, our case series suggests that secretory carcinomas exhibit a favorable clinical course and underscores the pivotal importance of distinguishing secretory carcinomas from other histological subtypes. [ABSTRACT FROM AUTHOR]

Certain undifferentiated round cell sarcomas displaying EWSR1::NFATC2 fusion have recently been reported, mostly in the bones. This report presents clinicopathological features of 3 additional EWSR1::NFATC2 fusion sarcomas of bone and soft tissues. We present 2 soft tissue and 1 bone tumors: A 62-year-old man with pain and a slowly growing, 8-cm-sized soft tissue mass in the anterolateral compartment of his right calf, along with multiple pulmonary metastatic lesions; a 63-year-old man with a 5-cm sized axillary mass of 4 months duration and a cystic renal mass; and a 53-year-old man with a complaint of leg pain was found to have a 2-cm diameter, intramedullary, lytic mass in the diaphysis of his left femur. Microscopic examination of the tumors in all patients revealed round to epithelioid cells arranged in cords and trabeculae in a myxohyaline stroma. Immunohistochemically, the tumor cells were positive for MIC2/CD99 (3/3), EMA (3/3), NKX3.1 (3/3), NKX2.2 (2/2), CD10 (2/2), and aggrecan (1/1), while negative for S100P and GFAP. Various keratins were also negative except focal AE1/AE3 positivity in the third tumor. By fluorescence in-situ hybridization, 2 tumors (#1 and #3) revealed EWSR1 gene rearrangement and amplification. Furthermore, 2 tumors (#1 and #2) displayed EWSR1ex8::NFATC2ex3 fusion with next-generation sequencing (NGS). The first patient was offered chemotherapy. However, he died of pulmonary metastasis. This report highlights the value of combining histopathological features and immunostains such as NXK3.1, NKX2.2, CD10, and aggrecan, along with EWSR1 testing for triaging these tumors for rare gene fusions by NGS that has prognostic implications. [ABSTRACT FROM AUTHOR]

Background: Trials and real‐life studies demonstrated clinically meaningful improvements of disease activity in the majority of patients with moderate to severe atopic dermatitis (AD) treated with the anti‐IL‐4RA‐antibody dupilumab. However, misdiagnosis or confounding skin diseases in particular cutaneous T‐cell lymphoma (CTCL) may lead to inadequate response. Objective: To investigate the clinical and pathological features of patients with AD who showed insufficient response to dupilumab. Methods: We reviewed the medical records of 371 patients treated with dupilumab for severe AD. Insufficient response was defined as failure to achieve an improvement of the eczema area severity index (EASI) of at least 50% (EASI‐50) at Week 16 and of 75% (EASI‐75) at Week 52. Among 46 patients with insufficient response, 35 patients consented to a re‐evaluation including a full physical exam, biopsies and laboratory assessments including immunohistochemistry and T‐cell receptor gene rearrangement analysis to differentiate CTCL. Results: Of the 371 patients treated with dupilumab, 46 (12.3%) patients showed insufficient response to dupilumab. Of these, 35 underwent further evaluation, and 19 (54.2% of inadequate responders) were finally diagnosed with mycosis fungoides (MF). In these patients, transition to or addition of conventional MF treatment led to clinical improvements. Conclusions: Insufficient response to dupilumab treatment may help uncover early MF on an existing AD background. [ABSTRACT FROM AUTHOR]

This document discusses recent advancements in sequencing technologies and their impact on research and clinical practice. It highlights improvements in short-read sequencing platforms, such as the NovaSeq X series, and the emergence of competitive alternatives to Illumina. The document also discusses advances in the analysis and interpretation of short-read sequencing data, as well as the advancements in long-read sequencing. It concludes by stating that these technological advancements will drive precision medicine and transform research, clinical practice, and healthcare. Additionally, the document mentions the use of RNA-seq, single-cell omics, spatial transcriptome profiling, and multi-omics approaches in understanding gene expression, tumor heterogeneity, and genome organization. [Extracted from the article]

Batracomorphus is the most diverse and widely distributed genus of Iassinae. Nevertheless, there has been no systematic analysis of the genome structure and phylogenetic relationships of the genus. To determine the characteristics of the mitogenomes of Batracomorphus species as well as the phylogenetic relationships between them, we sequenced and compared the mitogenomes of 11 representative Batracomorphus species. The results revealed that the mitogenomes of the 11 Batracomorphus species exhibited highly similar gene and nucleotide composition, and codon usage compared with other reported mitogenomes of Iassinae. Of these 11 species, we found that the mitogenomes of four species were rearranged in the region from trnI-trnQ-trnM to trnQ-trnI-trnM, whereas the remaining species presented a typical gene order. The topologies of six phylogenetic trees were in agreement. Eurymelinae consistently formed paraphyletic groups. Ledrinae and Evacanthinae formed sister taxa within the same clade. Similarly, Typhlocybinae and Mileewinae consistently clustered together. All phylogenetic trees supported the monophyly of Iassinae, indicating its evolutionary distinctiveness while also revealing its sister relationship with Coelidiinae. Notably, the nodes for all species of the genus Batracomorphus were well supported and these taxa clustered into a large branch that indicated monophyly. Within this large branch, four Batracomorphus species with a gene rearrangement (trnQ-trnI-trnM) exhibited distinctive clustering, which divided the large branch into three minor branches. These findings expand our understanding of the taxonomy, evolution, genetics, and systematics of the genus Batracomorphus and broader Iassinae groups. [ABSTRACT FROM AUTHOR]

Taiwanaptera montana is a apterous flat bug found in Yunnan Province, China. This study is the first to sequence, assemble, and annotate the complete mitochondrial genome of T. montana. The mitochondrial genome of T. montana has a total length of 15615 bp, which is a typical circular DNA, containing 13 protein-coding genes (PCGs), 22 tRNA genes, 2 rRNA genes and a control region, with A + T content of 69.4%. The phenomenon of gene rearrangement was found when the mitochondrial structure was compared with that of other Aradidae. The phylogenetic tree based on 37 mitochondrial genes showed that T. montana was most closely related to Libiocoris heissi. Aneurinae, Carventinae and Mezirinae are monophyletic groups. In addition, the results also confirmed that Aradinae and Calisiinae diverged earliest and were relatively primitive groups. [ABSTRACT FROM AUTHOR]

Double-hit lymphoma (DHL) formerly referred to high-grade B-cell lymphoma with concurrent MYC and BCL2 or BCL6 rearrangements, however, the updated 2022 World Health Organization Classification (5th edition online) excludes those with MYC and BCL 6 rearrangements from the high-grade category. DHL confined to the central nervous system (CNS), known as double-hit primary CNS lymphoma (DH-PCNSL), is rare with poorly understood clinical features. Here, we report a case of a 64-year-old man with multiple brain tumors diagnosed with DH-PCNSL who showed bone marrow (BM) infiltration early in the clinical course. The histological diagnosis was high-grade B-cell lymphoma with MYC and BCL6 rearrangements. Fluorodeoxyglucose positron emission tomography (FDG-PET) revealed no abnormal accumulation except in the CNS. The patient received whole-brain radiotherapy following the failure of high-dose methotrexate. After completion of radiotherapy, the patient developed thrombocytopenia, and BM biopsy showed infiltration of DHL cells, which were not detected by repeated FDG-PET. This is the first report of DH-PCNSL where identical gene rearrangements were confirmed in both the resected CNS tumor and BM tissue. Patients with DH-PCNSL require careful follow-up because they may be at a potential risk of BM infiltration, which may be undetectable by FDG-PET, particularly early in the disease course. [ABSTRACT FROM AUTHOR]

We collected 56 specimens of Laelaps chini from the endemic Hengduan Mountain rat species (Eothenomys miletus) and obtained the first complete mitochondrial genome of L. chini by next-generation sequencing (NGS). The L. chini mitogenome is 16,507 bp in size and contains 37 genes and a control region of 2380 bp in length. The L. chini mitogenome has a high AT content and a compact arrangement with four overlapping regions ranging from 1 to 2 bp and 16 spacer regions ranging from 1 to 48 bp. We analyzed 13 protein-coding genes of L. chini mitogenome and found that protein-coding genes in the L. chini mitogenome preferred codons ending in A/U and codon usage pattern was mainly influenced by natural selection. Cox1 has the slowest evolution rate and cox3 has the fastest evolution rate. We combined the mitochondrial genome of eight species of gamasid mites in the superfamily Dermanyssoidea from Genbank and the L. chini mitochondrial genome to analyze its rearrangement patterns and breakpoint numbers. We found that the L. chini mitogenome showed a novel arrangement pattern and nine species of gamasid mites in the superfamily Dermanyssoidea, which have been sequenced complete mitochondrial genomes to date, all showed different degrees of rearrangement. Laelaps chini, Echinolaelaps echidninus and Echinolaelaps fukinenensis were closely related species based on genetic distance and phylogenetic analyses. Notably they are clustered with Varroa destructor of the family Varroidae, suggesting that the family Varroidae is more closely related to the family Laelapidae, but more data are needed to test whether Varroa can be classified under the family Laelapidae. The L. chini mitogenome is the first complete mitochondrial genome for the genus Laelaps, and contributes to further exploration of the mitochondrial gene rearrangements and phylogeny for the superfamily Dermanyssoidea. [ABSTRACT FROM AUTHOR]

The species of Purpureocillium are cosmopolitan and multitrophic fungi that can infect a wide range of invertebrate hosts. This study reports the mitogenome of P. atypicola, a specialized spider pathogenic fungus. The 112,465 bp mitogenome encoded genes typically found in fungal mitogenomes, and a total of 52 introns inserted into seven genes. A comparison with three other Purpureocillium species revealed significant differences in length and intron number, primarily due to intron variation; however, there was no dynamic variation in the introns of the cox1 gene within the same species of the Purpureocillium genus. Different mitochondrial protein-coding genes showed variable degrees of genetic differentiation among these species, but they were all under purifying selection. Additionally, frequent intron loss or gain events were detected to have occurred during the evolution of the Ophiocordycipitaceae mitogenomes, yet the gene arrangement remains conserved. A phylogenetic analysis of the combined mitochondrial gene set gave identical and well-supported tree topologies. The estimated age of the crown of Ophiocordycipitaceae and Purpureocillium were around the Early Cretaceous period (127 Mya) and Late Cretaceous period (83 Mya), respectively. The results of this study advance our understanding of the genomics, evolution, and taxonomy of this important fungal group. [ABSTRACT FROM AUTHOR]

To evaluate the expression of recombinant activating gene (RAG) and B cell receptor (BCR) gene rearrangements in mature peripheral B lymphocytes in Takayasu arteritis (TA) to explore the possible mechanism of humoral immune response in TA. Ten patients with TA and 10 age‐ and sex‐matched healthy volunteers (control group) from Beijing Shijitan Hospital, Capital Medical University and Peking Union Medical College Hospital, between 2022 and 2023, were included in this study. The mRNA of the RAG was measured using real‐time quantitative PCR (RT‐PCR). Western blotting was used to detect RAG protein expression levels. NGS technology was used to detect BCR gene rearrangement. The mRNA expression level of RAG1 and RAG2 in peripheral mature B lymphocytes in patients with TA was significantly higher than in the control group (RAG1 5.56 ± 1.71 vs. 1.94 ± 0.86, p < 0.05; RAG2 5.26 ± 1.59 vs. 1.65 ± 0.64, p < 0.05), respectively. The protein expression level of the RAG1 and the RAG2 in peripheral mature B lymphocytes in patients with TA was significantly higher than in the healthy control group (RAG1 4.33 ± 1.58 vs. 1.52 ± 0.59, p < 0.001; RAG2 4.67 ± 1.88 vs. 1.59 ± 0.56, p < 0.001). The number of peripheral B lymphocyte BCR clonotypes in the group of patients with TA was significantly higher than in the normal control group (1574 ± 317.7 vs. 801.3 ± 202.1, p < 0.05). The abundance of IGHV clones in patients with TA was higher than in the normal control group (31.185% vs. 13.449%), which was positively correlated with the expression levels of RAG1 and RAG2 (correlation coefficient r = 1.00, p < 0.001), respectively. High expression of the RAG gene coexists with secondary BCR gene rearrangement in mature peripheral B lymphocytes in patients with TA, providing important clues regarding the potential humoral response in TA; however, further studies with larger samples are needed. [ABSTRACT FROM AUTHOR]

Background: Perivascular epithelioid cell tumours (PEComas) are soft tissue tumours. These neoplasms belong to the family of mesenchymal tumours, which include angiomyolipomas, clear-cell sugar tumours of the lung, and PEComas not otherwise specified (NOS). The probability of a perivascular epithelioid cell tumour (PEComa) occurring in the uterus is low, and the incidence, diagnosis, treatment, and outcomes of such tumours are still unclear. Case presentation: A 51-year-old woman presented a 4-year history of natural menopause. An intrauterine mass was detected via ultrasound examination; the mass showed a tendency to increase but caused no symptoms. The levels of tumour markers were within the normal range. Pathological analysis of the curettage revealed perivascular epithelioid differentiation of the endometrial tumour. Consequently, a laparoscopic total hysterectomy with bilateral adnexectomy was performed. No distant metastasis was detected via whole-body positron emission computed tomography (PETCT) after the operation. Fluorescence in situ hybridization (FISH) revealed no TFE3 gene rearrangement. Next-generation sequencing of bone and soft tissue revealed negative TSC1/2 and TP53 expression. No recurrence or metastasis was observed during the 18-month follow-up period. Conclusion: PEComa of the gynecologic tract is a rare and challenging entity. Diffuse HMB-45 expression, TSC alterations and TFE3 rearrangement are characteristic of uterine PEComas. Surgical resection is the first choice. Genetic testing is helpful for determining the nature of the mass and for choosing targeted therapy. Further research is needed to establish treatment protocols. [ABSTRACT FROM AUTHOR]

The yellow–flowered Spathoglottis aurea (tribe Collabieae; family Orchidaceae) is native to the mountainous areas of Peninsular Malaysia. The species is well known as an ornamental plant and for its role in artificial hybrid breeding. There is an interesting evolutionary relationship between S. aurea and the geographically isolated S. microchilina from Borneo that has encouraged further study of the S. aurea populations, but the genomic resource for S. aurea has not yet been reported. The present study reports the first work to characterize a chloroplast (cp) genome among the Spathoglottis genus. The complete cp genome of S. aurea was assembled from a sequence generated by the Illumina platform and analysed in comparison with other Collabieae species available in the GenBank database. The cp genome of S. aurea is 157,957 base pairs (bp) in length with guanine-cytosine (GC) content of 37.3%. The genome possessed a typical quadripartite cp genome structure with large single-copy (LSC) (86,888 bp), small single-copy (SSC) (18,125 bp) and inverted repeat (IR) (26,472 bp) sequences. A total of 134 genes were annotated, with 88 protein coding genes (PCGs), 38 transfer RNA (tRNA) genes and eight ribosomal RNA (rRNA) genes. Overall, 80 simple sequence repeats (SSR) or microsatellites were identified. Comparative analysis with other Collabieae species revealed high conservation in the cp genome arrangements with minimal difference in genome lengths. However, several mutational hotspots were also detected, with high potential to be developed as genetic markers for phylogenetic analysis. Characterization of the S. aurea cp genome revealed its conserved nature without gene loss or rearrangements when compared to other species of the Collabieae tribe. Phylogenetic analysis of Collabieae species also revealed that S. aurea has a distant evolutionary relationship to other members of the Collabieae species, despite the presence of problematic genera such as Phaius and Cephalantheropsis. [ABSTRACT FROM AUTHOR]

Modern sequencing technology enables the systematic detection of complex structural variation (SV) across genomes. However, extensive DNA rearrangements arising through a series of mutations, a phenomenon we refer to as serial SV (sSV), remain underexplored, posing a challenge for SV discovery. Here, we present NAHRwhals (https://github.com/WHops/NAHRwhals), a method to infer repeat-mediated series of SVs in long-read genomic assemblies. Applying NAHRwhals to haplotype-resolved human genomes from 28 individuals reveals 37 sSV loci of various length and complexity. These sSVs explain otherwise cryptic variation in medically relevant regions such as the TPSAB1 gene, 8p23.1, 22q11 and Sotos syndrome regions. Comparisons with great ape assemblies indicate that most human sSVs formed recently, after the human-ape split, and involved non-repeat-mediated processes in addition to non-allelic homologous recombination. NAHRwhals reliably discovers and characterizes sSVs at scale and independent of species, uncovering their genomic abundance and suggesting broader implications for disease. Structural variants (SV) can accumulate in repeat-rich parts of the genome and transform them in unexpected ways. Here, with their new assembly-based genotyper (NAHRwhals), the authors verify multi-step SVs in 37 human loci and identify alleles at risk for copy-number variation. [ABSTRACT FROM AUTHOR]

Cats have the highest incidence of lymphoma among all animal species. Lymphoma accounts for 41% of all malignant tumors in cats and is responsible for 90% of hematopoietic tumors in felines. Biopsies are considered the gold standard for diagnosis. Polymerase chain reaction (PCR)-based clonality assessment of antigen receptor gene rearrangements can be a valuable complementary tool for identifying infiltrating B-and T-lymphocyte clones. Many studies have focused on intestinal cases but few have addressed mediastinal lymphoma. This study aims to: (1) investigate the clonality patterns of lymphoma samples from various anatomical sites, with a particular focus on mediastinal lymphoma, and (2) evaluate the sensitivity and specificity of the clonality analysis of pleural effusion samples in comparison with cytology, histology, immunohistochemistry, and immunocytochemistry for diagnosing mediastinal lymphoma. There were 82 cases, divided into 49 formalin-fixed and paraffin-embedded biopsy specimens (FFPE), 22 cell pellets, and 11 fresh tissue. This study examined the sensitivity and specificity of PCR for antigen receptor rearrangement (PARR) compared to immunohistochemistry (IHC) and immunocytochemistry. For T-cell receptor gamma chain genes, PARR demonstrated a sensitivity of 58.33% for both fresh tissue and FFPE samples, with a specificity of 100%. Cell pellet analysis exhibited a sensitivity of 64.71% and maintained 100% specificity. A combined analysis of fresh tissue and FFPE with cell pellets showed a sensitivity of 62.07%. For IGH, the sensitivity for fresh tissue and FFPE samples was 56.25%, while cell pellet analysis showed a sensitivity of 62.50%. When considering fresh tissue and FFPE samples, the sensitivity was 57.14%. In conclusion, molecular techniques have emerged as valuable tools for detecting lymphoma, especially in cases where traditional diagnostic methods yield inconclusive results, such as mediastinal lymphoma. While biopsy may not always be feasible, cytology and cell pellets obtained from pleural effusion offer alternative immunocytochemistry and molecular analysis samples, provided they are of sufficient quality and quantity. All sample types considered in this study were suitable for PARR to aid in cases with inconclusive results. Therefore, the sample selection should be tailored to the clinical situation. [ABSTRACT FROM AUTHOR]

The article discusses a rare subtype of non-Hodgkin lymphoma called Large B‐cell lymphoma with IRF4‐rearrangement (LBL‐IRF4R), which predominantly affects children and younger adults. The case study presented in the article highlights the challenges in diagnosing this subtype and the importance of incorporating new technologies like Hi‐C sequencing for more comprehensive molecular analysis. The study also reveals potential genetic mutations associated with LBL‐IRF4R and the implications for diagnosis and treatment. Overall, the article emphasizes the significance of integrating classic histopathologic diagnosis with advanced molecular techniques in understanding and managing rare hematological neoplasms. [Extracted from the article]

The mitochondrial DNA (mtDNA) of bumblebees (Bombus) has been widely used for phylogenetic studies, but its evolution is still underexplored. Here we report a comprehensive analysis of 60 bumblebee mitogenomes, including 40 newly assembled ones, to investigate bumblebee mtDNA structure, composition, and informativeness under a phylogenetic framework. Our mtDNA dataset supports the monophyly of Bombus and its subgenera, although we found a high degree of tree discordance in deeper nodes when using different inference methods or matrix composition. Concerning mitogenome structure, our results show that tRNA genes were often rearranged, with unique rearrangements indicating shared ancestry across bumblebee subgenera, illustrating their potential for subgeneric classification. Our results also challenge the notion that faster evolving mtDNA exhibits higher gene rearrangement rates. Finally, we explicitly assessed shifts in selection constraints of mtDNA genes in obligate social parasites of subgenus Psithyrus and found that their mtDNA evolved under relaxed selective constraints. Our findings show the utility of mtDNA in providing insights into bumblebee phylogenetics, evolution, and genome trait diversification. We also highlight the potential for comparative mitogenomics to uncover previously unknown aspects of bumblebee evolution, offering exciting opportunities for future research in this field. [ABSTRACT FROM AUTHOR]

Simple Summary: A total of 37 mitochondrial genes appears in a certain arrangement in most insects, and the transcription of this conserved mitochondrial genome (mitogenome) has been well-studied in species like Drosophila melanogaster, Erthesina fullo and Coridius chinensis. However, transcription of the mitogenome with extensive gene rearrangement has rarely been studied. In this research, we sequenced the mitogenome and mitochondrial transcriptome of Sericothrips houjii (Thysanoptera: Thripidae: Sericothripinae). The mitogenome of S. houjii exhibited extensive gene rearrangement and contained two control regions (CRs) with sequence repeats. Compared to the insect mitogenome with a typical gene order, the mitogenomic feature, relative gene expression level, transcriptional model and post-transcriptional cleavage of S. houjii were quite different. Unlike other insects where ribosomal RNA (rRNA) is typically highly expressed, ND4/ND4L in S. houjii exhibits the highest expression. Both strands of this mitogenome were entirely transcribed and the bicistronic messenger RNA (mRNA) COI/ND3 was reported for the first time in insects. Our study provides new insights into the transcriptional and post-transcriptional regulation processes in the insect mitogenome with extensive gene rearrangement and duplicated CRs. The mitochondrial genome (mitogenome) of Thysanoptera has extensive gene rearrangement, and some species have repeatable control regions. To investigate the characteristics of the gene expression, transcription and post-transcriptional processes in such extensively gene-rearranged mitogenomes, we sequenced the mitogenome and mitochondrial transcriptome of Sericothrips houjii to analyze. The mitogenome was 14,965 bp in length and included two CRs contains 140 bp repeats between COIII-trnN (CR1) and trnT-trnP (CR2). Unlike the putative ancestral arrangement of insects, S. houjii exhibited only six conserved gene blocks encompassing 14 genes (trnL2-COII, trnD-trnK, ND2-trnW, ATP8-ATP6, ND5-trnH-ND4-ND4L and trnV-lrRNA). A quantitative transcription map showed the gene with the highest relative expression in the mitogenome was ND4-ND4L. Based on analyses of polycistronic transcripts, non-coding RNAs (ncRNAs) and antisense transcripts, we proposed a transcriptional model of this mitogenome. Both CRs contained the transcription initiation sites (TISs) and transcription termination sites (TTSs) of both strands, and an additional TIS for the majority strand (J-strand) was found within antisense lrRNA. The post-transcriptional cleavage processes followed the "tRNA punctuation" model. After the cleavage of transfer RNAs (tRNAs), COI and ND3 matured as bicistronic mRNA COI/ND3 due to the translocation of intervening tRNAs, and the 3′ untranslated region (UTR) remained in the mRNAs for COII, COIII, CYTB and ND5. Additionally, isoform RNAs of ND2, srRNA and lrRNA were identified. In summary, the relative mitochondrial gene expression levels, transcriptional model and post-transcriptional cleavage process of S. houjii are notably different from those insects with typical mitochondrial gene arrangements. In addition, the phylogenetic tree of Thripidae including S. houjii was reconstructed. Our study provides insights into the phylogenetic status of Sericothripinae and the transcriptional and post-transcriptional regulation processes of extensively gene-rearranged insect mitogenomes. [ABSTRACT FROM AUTHOR]

The ever-growing knowledge regarding NSCLC molecular biology has brought innovative therapies into clinical practice; however, the treatment situation in the non-metastatic setting is rapidly evolving. Indeed, immunotherapy-based perioperative treatments are currently considered the standard of care for patients with resectable NSCLC in the absence of EGFR mutations or ALK gene rearrangements. Recently, data have been presented on the use of tyrosine kinase inhibitors (TKIs) in the adjuvant and locally advanced setting for patients with NSCLC harboring such driver gene alterations. The aim of the current work is to review the available evidence on the use of targeted treatments in the non-metastatic setting, together with a summary of the ongoing trials designed for actionable gene alterations other than EGFR and ALK. To date, 3-year adjuvant osimertinib treatment has been demonstrated to improve DFS and OS and to reduce CNS recurrence in resected EGFR-mutated NSCLC in stage IB–IIIA (TNM 7th edition). The use of osimertinib after chemo-radiation in stage III unresectable EGFR-mutated NSCLC showed the relevant PFS improvement. In the ALK-positive setting, 2-year alectinib treatment was shown to clearly improve DFS compared to adjuvant standard chemotherapy in resected NSCLC with stage IB (≥4 cm)–IIIA (TNM 7th edition). Several trials are ongoing to establish the optimal adjuvant TKI treatment duration, as well as neoadjuvant TKI strategies in EGFR- and ALK-positive disease, and (neo)adjuvant targeted treatments in patients with actionable gene alterations other than EGFR or ALK. In conclusion, our review depicts how the current treatment scenario is expected to rapidly change in the context of non-metastatic NSCLC with actionable gene alterations, hence appropriate molecular testing from the early stages has become crucial to establish the most adequate approaches both in the perioperative and the locally advanced disease. [ABSTRACT FROM AUTHOR]

Ewing-like sarcomas (ELS) are round cell mesenchymal neoplasms that are highly aggressive to bone and/or soft tissue. However, they rarely occur in the nose, with no reported such cases in the medical literature to date. Here, we reported the case of a two-year-old Chinese boy who presented with a mass in the left nasal cavity. Surprisingly, the final histopathological diagnosis of the nasal mass was determined to be a subtype of ELS, BCOR -rearranged sarcoma. Therefore, we retrospectively analyzed the clinical data of this case and reviewed the relevant literature on ELS and BCOR -rearranged sarcoma. The purpose of this article is to provide new insights into the clinical characteristics of children with BCOR -rearranged Ewing-like sarcoma and to improve the understanding of this disease. [ABSTRACT FROM AUTHOR]

Mutating replication-dependent (RD) histone genes is an important tool for understanding chromatin-based epigenetic regulation. Deploying this tool in metazoans is particularly challenging because RD histones in these organisms are typically encoded by many genes, often located at multiple loci. Such gene arrangements make the ability to generate homogenous histone mutant genotypes by site-specific gene editing quite difficult. Drosophila melanogaster provides a solution to this problem because the RD histone genes are organized into a single large tandem array that can be deleted and replaced with transgenes containing mutant histone genes. In the last ∼15 years several different RD histone gene replacement platforms were developed using this simple strategy. However, each platform contains weaknesses that preclude full use of the powerful developmental genetic capabilities available to Drosophila researchers. Here we describe the development of a newly engineered platform that rectifies many of these weaknesses. We used CRISPR to precisely delete the RD histone gene array (HisC), replacing it with a multifunctional cassette that permits site-specific insertion of either one or two synthetic gene arrays using selectable markers. We designed this cassette with the ability to selectively delete each of the integrated gene arrays in specific tissues using site-specific recombinases. We also present a method for rapidly synthesizing histone gene arrays of any genotype using Golden Gate cloning technologies. These improvements facilitate the generation of histone mutant cells in various tissues at different stages of Drosophila development and provide an opportunity to apply forward genetic strategies to interrogate chromatin structure and gene regulation. [ABSTRACT FROM AUTHOR]

Several reports of concurrent MYC , BCL2 , BCL6 , and CCND1 rearrangements in high-grade B-cell lymphoma (HGBL) have been recently described. Herein, we aimed to delineate the scope of this entity through a review of HGBL with a "quadruple-hit" genetic profile identified at our institution. We performed a retrospective review (2015-2023) at our institution of B-cell lymphoma (BCL) cases that were evaluated with concurrent MYC , BCL2 , and BCL6 break-apart and IGH::MYC and IGH::CCND1 dual-color dual-fusion fluorescence in situ hybridization studies. Of 203 cases meeting inclusion criteria, 2 (1%) with a quadruple-hit genetic profile were identified. Case 1 represented a 59-year-old female with widespread lymphadenopathy and a diagnosis of HGBL who exhibited primary refractoriness to dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab (DA-EPOCH-R) chemotherapy. Case 2 represented a 58-year-old male with mediastinal and abdominal lymphadenopathy and a diagnosis of large BCL who died from disease after 1 cycle of DA-EPOCH-R chemotherapy. Similarly, a literature review of 7 previously reported cases of HGBL with a quadruple-hit profile also demonstrated aggressive disease behavior. Our study adds 2 new cases to the rarely encountered quadruple-hit HGBL, and a brief meta-analysis of the 9 available cases indicates aggressive disease behavior conferred by this constellation of genetic events. [ABSTRACT FROM AUTHOR]

This article discusses a case study of a rare tumor called juvenile trabecular ossifying fibroma (JTOF). The study found that JTOF can have similar genetic alterations to another type of tumor called psammomatoid ossifying fibroma (PsOF), specifically rearrangements in the SATB2 gene. The patient in the case study was a 12-year-old girl who had a rapidly growing mandibular lesion. The tumor was surgically removed, and genetic analysis revealed SATB2 gene rearrangements. This expands our understanding of the molecular landscape of JTOF and suggests that SATB2 anomalies may play a role in the development of these tumors. Further research is needed to fully understand the genetic factors involved in JTOF. [Extracted from the article]

The underlying processes behind the formation, evolution, and long-term maintenance of multiple sex chromosomes have been largely neglected. Among vertebrates, fishes represent the group with the highest diversity of multiple sex chromosome systems and, with six instances, the Neotropical fish genus Harttia stands out by presenting the most remarkable diversity. However, although the origin mechanism of their sex chromosome systems is well discussed, little is known about the importance of some repetitive DNA classes in the differentiation of multiple systems. In this work, by employing a combination of cytogenetic and genomic procedures, we evaluated the satellite DNA composition of H. carvalhoi with a focus on their role in the evolution, structure, and differentiation process of the rare XY1Y2 multiple-sex chromosome system. The genome of H. carvalhoi contains a total of 28 satellite DNA families, with the A + T content ranging between 38.1% and 68.1% and the predominant presence of long satellites. The in situ hybridization experiments detected 15 satellite DNAs with positive hybridization signals mainly on centromeric and pericentromeric regions of almost all chromosomes or clustered on a few pairs. Five of them presented clusters on X, Y1, and/or Y2 sex chromosomes which were therefore selected for comparative hybridization in the other three congeneric species. We found several conserved satellites accumulated on sex chromosomes and also in regions that were involved in chromosomal rearrangements. Our results provide a new contribution of satellitome studies in multiple sex chromosome systems in fishes and represent the first satellitome study for a Siluriformes species. [ABSTRACT FROM AUTHOR]