Mutations In Gene Research Articles

Mycobacterium tuberculosis evolution from monoresistance to pre-extensive drug resistance during a prolonged household outbreak

Whole genome sequencing (WGS) is sensitive tool for the analysis of tuberculosis transmission and drug-resistance. We used WGS to analyze the Mycobacterium tuberculosis evolution from isoniazid monoresistance to MDR/preXDR during a prolonged household outbreak. The outbreak started with a isoniazid resistant strain (katG S315T mutation) and evolve in two cases to pre-XDR phenotype (with mutations in katG, rpoB, embB, pncA and gyrA genes). Based on WGS data and epidemiological interview we proposed a possible chain of transmission an evolution of the strains.Similar intra-patient and inter-patient acquisition of variability was observed, making difficult to distinguish reinfection or reactivation. Analysis of WGS data together with epidemiological clinical history are discussed in order to distinguish between prolonged infections or transition from latency to reactivation. Classical interview and clinical history taking should be consider to fully understanding WGS data. With a still low incidence of TB cases, Uruguay could use universal WGS of all isolates to reduce time of diagnosis, detect outbreaks and perform public actions to reduce TB incidence.

CRISPR/Cas9-mediated generation of a human induced pluripotent stem cell line with PRPF6 c.2699 G > A mutation to model retinitis pigmentosa

PRPF6, located on chromosome 20, is required for the formation of the spliceosome. Mutations in the PRPF6 gene can lead to retinitis pigmentosa (RP), a common inherited retinal disease characterized by progressive degeneration of retinal pigment epithelium and photoreceptors. Here, we generated an induced pluripotent stem cell (iPSC) line carrying the PRPF6 c.2699 G > A mutation using CRISPR/Cas9 technology, which will provide a valuable resource for RP pathogenesis and treatment research.

The Manifestations and Complications of X-linked Hypophosphatemia in Saudi Arabia: A Retrospective Study

Background: X-linked hypophosphatemia (XLH) is a genetic disease of phosphate metabolism in which inactivating mutations of the phosphate regulating endopeptidase homolog, X-linked (PHEX) gene lead to local and systemic effects. In our pediatric clinics, XLH was observed to be associated with multiple complications despite conventional treatment. There is a need for novel treatment modalities to prevent disease progression and aid in the resolution of symptoms. Methods: This retrospective cross-sectional study aimed to understand the manifestations and complications of XLH in patients followed up at the endocrinology clinics in King Faisal Specialist Hospital and Research Center in Saudi Arabia. The study was conducted by reviewing the medical files of all XLH patients at the King Faisal Specialist Hospital and Research Center. Results: All the patients (N=24) who were included in this study had PHEX gene mutations. The mean age was 18.7 13.6 years and 68% were females. The mean height standard deviation score (HSDS) was ‑2.96 (-5.25 to -0.97) and 12 patients reached their final height (mean final HSDS, -3.28 [-1.39 to ‑5.39]). Skeletal deformities (mainly genu varum) were observed in 68% of the patients and 29% had craniosynostosis; 54% had undergone corrective osteotomy. Hyperparathyroidism was observed in 54% of the patients and 45% of the patients had nephrocalcinosis (grades 2/3). Conclusions: In our study, a majority of the XLH patients suffered from complications arising from the use of conventional therapy, thus indicating the need for novel treatment modalities for these patients. Additionally, no correlation between genotype and phenotype was found.

Late-onset primary muscle diseases mimicking sarcopenia.

Sarcopenia is an age-related loss of skeletal muscle mass, strength, and function that causes various health problems. In contrast, late-onset primary myopathies, which occur in the older population, are caused by a variety of factors, including genetic mutations, autoimmune processes, and metabolic abnormalities. Although sarcopenia and primary myopathy are two distinct disease processes, their symptoms can overlap, making differentiation challenging. The diagnostic criteria for sarcopenia have evolved over time, and various criteria have been proposed by expert groups. Late-onset primary muscle diseases such as inclusion body myositis, sporadic late-onset nemaline myopathy, muscular dystrophies, distal myopathies, myofibrillar myopathies, metabolic myopathies, and mitochondrial myopathies share common pathogenic mechanisms with sarcopenia, further complicating the diagnostic process. Appropriate clinical evaluation, including detailed history-taking, physical examination, and diagnostic testing, is essential for accurate diagnosis and management. Treatment approaches, including exercise, nutritional support, and disease-specific therapies, must be tailored to the characteristics of each disease. Despite these differences, sarcopenia and primary myopathies require careful consideration in the clinical setting for proper diagnosis and management. This review outlines the evolution of diagnostic criteria and diagnostic items for sarcopenia, late-onset primary myopathies that should be differentiated from sarcopenia, common pathomechanisms, and diagnostic algorithms to properly differentiate primary myopathies. Geriatr Gerontol Int 2024; ••: ••-••.

Genome sequencing analysis of the pncA, rpsA and panD genes responsible for pyrazinamide resistance of Mycobacterium tuberculosis from Indonesian isolates.

Developing the most suitable treatment against tuberculosis based on resistance profiles is imperative to effectively cure tuberculosis patients. Whole-genome sequencing is a molecular method that allows for the rapid and cost-effective detection of mutations in multiple genes associated with anti-tuberculosis drug resistance. This sequencing approach addresses the limitations of culture-based methods, which may not apply to certain anti-TB drugs, such as pyrazinamide, because of their specific culture medium requirements, potentially leading to biased resistance culture results. Thirty-four M. tuberculosis isolates were subcultured on a Lowenstein-Jensen medium. The genome of these bacteria was subsequently isolated using cetyltrimethylammonium bromide. Genome sequencing was performed with Novaseq Illumina 6000 (Illumina), and the data were analysed using the GenTB and Mykrobe applications. We also conducted a de novo analysis to compare the two methods and performed mutation analysis of other genes encoding pyrazinamide resistance, namely rpsA and panD. The results revealed mutations in the pncA gene, which were identified based on the databases accessed through GenTB and Mykrobe. Two discrepancies between the drug susceptibility testing and sequencing results may suggest potential instability in the drug susceptibility testing culture, specifically concerning PZA. Meanwhile, the results of the de novo analysis showed the same result of pncA mutation to the GenTB or Mykrobe; meanwhile, there were silent mutations in rpsA in several isolates and a point mutation; no mutations were found in the panD gene. However, the mutations in the genes encoding pyrazinamide require further and in-depth study to understand their relationship to the phenotypic profile. Compared to the conventional culture method, the whole-genome sequencing method has advantages in determining anti-tuberculosis resistance profiles, especially in reduced time and bias.

Holomics and Artificial Intelligence-Driven Precision Oncology for Medullary Thyroid Carcinoma: Addressing Challenges of a Rare and Aggressive Disease.

Background/Objective: Medullary thyroid carcinoma (MTC) is a rare yet aggressive form of thyroid cancer comprising a disproportionate share of thyroid cancer-related mortalities, despite its low prevalence. MTC differs from other differentiated thyroid malignancies due to its heterogeneous nature, presenting complexities in both hereditary and sporadic cases. Traditional management guidelines, which are designed primarily for papillary thyroid carcinoma (PTC), fall short in providing the individualized care required for patients with MTC. In recent years, the sheer volume of data generated from clinical evaluations, radiological imaging, pathological assessments, genetic mutations, and immunological profiles has made it humanly impossible for clinicians to simultaneously analyze and integrate these diverse data streams effectively. This data deluge necessitates the adoption of advanced technologies to assist in decision-making processes. Holomics, which is an integrated approach that combines various omics technologies, along with artificial intelligence (AI), emerges as a powerful solution to address these challenges. Methods: This article reviews how AI-driven precision oncology can enhance the diagnostic workup, staging, risk stratification, management, and follow-up care of patients with MTC by processing vast amounts of complex data quickly and accurately. Articles published in English language and indexed in Pubmed were searched. Results: AI algorithms can identify patterns and correlations that may not be apparent to human clinicians, thereby improving the precision of personalized treatment plans. Moreover, the implementation of AI in the management of MTC enables the collation and synthesis of clinical experiences from across the globe, facilitating a more comprehensive understanding of the disease and its treatment outcomes. Conclusions: The integration of holomics and AI in the management of patients with MTC represents a significant advancement in precision oncology. This innovative approach not only addresses the complexities of a rare and aggressive disease but also paves the way for global collaboration and equitable healthcare solutions, ultimately transforming the landscape of treatment and care of patients with MTC. By leveraging AI and holomics, we can strive toward making personalized healthcare accessible to every individual, regardless of their economic status, thereby improving overall survival rates and quality of life for MTC patients worldwide. This global approach aligns with the United Nations Sustainable Development Goal 3, which aims to ensure healthy lives and promote well-being at all ages.

Type 1 Hyperphosphatemic Familial Tumoral Calcinosis Associated With a Homozygous Variant Mutation in the GALNT3 Gene

Type 1 Hyperphosphatemic Familial Tumoral Calcinosis Associated With a Homozygous Variant Mutation in the GALNT3 Gene

Therapeutic Options for Crigler–Najjar Syndrome: A Scoping Review

Crigler–Najjar Syndrome (CNS) is a rare genetic disorder caused by mutations in the UGT1A1 gene, leading to impaired bilirubin conjugation and severe unconjugated hyperbilirubinemia. CNS presents in the following forms: CNS type 1 (CNS1), the more severe form with the complete absence of UGT1A1 activity, and CNS type 2 (CNS2), with partial enzyme activity. This narrative review aims to provide a detailed overview of CNS, highlighting its clinical significance and the need for new, more effective treatments. By summarizing current knowledge and discussing future treatments, this article seeks to encourage further research and advancements that can improve outcomes for CNS patients. The literature analysis showed that CNS1 requires aggressive management, including phototherapy and plasmapheresis, but liver transplantation (LT) remains the only definitive cure. The timing of LT is critical, as it must be performed before the onset of irreversible brain damage (kernicterus), making early intervention essential. However, LT poses risks such as graft rejection and lifelong immunosuppression. CNS2 is milder, with patients responding well to phenobarbital and having a lower risk of kernicterus. Recent advancements in gene therapy and autologous hepatocyte transplantation offer promising alternatives to LT. Gene therapy using adeno-associated virus (AAV) vectors has shown potential in preclinical studies, though challenges remain in pediatric applications due to liver growth and pre-existing immunity. Autologous hepatocyte transplantation avoids the risk of rejection but requires further research. These emerging therapies provide hope for more effective and less invasive treatment options, aiming to improve the quality of life for CNS patients and reduce reliance on lifelong interventions.

Dendrosomal Curcumin Showed Cytotoxic Effects on Breast Cancer Cell Line by Inducing Mitochondrial Apoptosis Pathway and Cell Division Arrest

Background: Mutations in the p53 gene have been linked to the initiation and progression of breast cancer, as well as resistance to chemotherapy. Therefore, the development of novel treatment approaches is essential to combat this disease. Objectives: This study aimed to evaluate the effects of dendrosomal curcumin (DNC) on the breast cancer cell line MDA-MB231. Methods: MDA-MB231 cells were treated with 20 μM DNC, and the apoptosis rate and cell proliferation cycles were assessed using flow cytometry. Additionally, after RNA extraction and cDNA synthesis, the expression levels of Lnc-DANCR, EZH2, Noxa, bcl-2, bax, PUMA, p21, and p53 genes were analyzed using RT-PCR. Protein expression levels of P53, P21, Bcl-2, and Bax were evaluated through western blotting. Results: Dendrosomal curcumin induced apoptosis in MDA-MB231 cells and caused cell cycle arrest at the SubG1 phase. Dendrosomal curcumin treatment downregulated Lnc-DANCR, EZH2, bcl-2, and p53 gene expression, while upregulating bax, Noxa, PUMA, and p21 gene expression in a time-dependent manner. Bax and P21 protein levels were significantly upregulated following DNC treatment, whereas Bcl-2 and P53 protein levels were downregulated in DNC-treated breast cancer cells. Conclusions: In summary, dendrosomal nanocurcumin demonstrated potent anti-tumor effects against breast cancer cells, suggesting its potential as a therapeutic agent in breast cancer treatment.

Analysis of Calcium-Sensing Receptor Signaling Using Dual Luciferase Assays.

Luciferases catalyze a reaction that involves the emission of light, a phenomenon referred to as "bioluminescence". The calcium-sensing receptor (CaSR), a G protein-coupled receptor (GPCR), induces characteristic signaling pathways that stimulate extracellular signal-regulated kinase 1/2 (ERK1/2) and Ca2+ mobilization from the endoplasmic reticulum. ERK1/2 causes an activation of the serum response element (SRE), whereas Ca2+ causes an activation of the nuclear factor of activated T-cells response element (NFAT-RE). Transfection of cells with a vector containing a firefly luciferase reporter gene under the control of the SRE or NFAT-RE allows the monitoring of ERK1/2 activation and Ca2+ mobilization, respectively, by measuring luminescence. In a dual luciferase assay, firefly luminescence is normalized by co-transfecting an internal control vector, which contains a constitutively active promoter driving the expression of a second luciferase, namely, Renilla luciferase, whose activity can be quantified within the same sample. Here, a protocol for the analysis of CaSR signaling using dual luciferase assays in HEK293 cells is provided. The assays can, for example, be used to investigate functional consequences of mutations in the CaSR gene.

Possibilities for diagnosing essential thrombocythemia at the stage of primary health care

This clinical case presents a 39-year-old woman diagnosed with essential thrombocythemia, accompanied by a review of the epidemiology, clinical and diagnostic criteria, and patient management strategies. The case also includes a discussion of potential complications and prognosis associated with the condition. The importance of thorough outpatient monitoring is emphasized, which should include regular assessments of clinical symptoms, changes in blood count parameters, bone marrow trephine biopsy, and molecular genetic testing for MPL and CALR gene mutations. The report highlights gaps in the current medical examination process, suggesting that addressing these deficiencies could improve early detection of essential thrombocythemia and enable timely pathogenetic therapy with antiplatelet agents to prevent complications.

The Clinical and Molecular Landscape of Rosette-Forming Glioneuronal Tumors.

Rosette-Forming Glioneuronal Tumors (RGNTs) are rare, typically benign central nervous system tumors primarily located in the fourth ventricle and pineal region. Despite being classified as WHO grade I with generally favorable prognoses, RGNTs present complexities in their molecular mechanisms, occasional malignant transformation, and epidemiological characteristics that require further investigation. This study systematically reviews the existing literature to analyze the epidemiological patterns, MRI characteristics, pathological features, diagnostic challenges, and molecular mechanisms associated with RGNTs, aiming to provide a comprehensive theoretical foundation for clinical practice and future research. Through an in-depth review of recent studies, key molecular mechanisms, including mutations in FGFR1, PIK3CA, TERT, and IDH1/2, are highlighted. Additionally, the challenges in accurate diagnosis and the potential for misdiagnosis are discussed, emphasizing the importance of thorough molecular analysis in clinical settings. The literature indicates that RGNTs predominantly affect young adults and adolescents, with a slight female predominance. MRI typically reveals mixed cystic-solid lesions, often accompanied by hydrocephalus. Pathologically, RGNTs are characterized by a combination of neuronal and glial components, with immunohistochemical staining showing positivity for Synaptophysin and GFAP. High frequencies of FGFR1 and PIK3CA mutations underscore the significance of these pathways in RGNT pathogenesis and progression. Although RGNTs generally exhibit low malignancy, the TERT mutations identified in some cases suggest a risk of malignant transformation. This study concludes that while current treatment strategies focus on surgical resection, integrating molecular diagnostics and targeted therapies may be essential for managing recurrent or refractory RGNTs. Future research should explore the impact of various gene mutations on tumor behavior and their correlation with clinical outcomes, to optimize individualized therapeutic strategies and improve patient survival and quality of life.

The prognostic and immune significance of Rab11A in pan-cancer and its function and mechanism underlying estrogen receptor targeting in breast cancer.

Rab11A is an important molecule for recycling endosomes and is closely related to the proliferation, invasion, and metastasis of tumors. This study investigated the prognostic and immune significance of Rab11A and validated its potential function and mechanism in breast cancer (BRCA). RNA sequencing data for 33 tumors were downloaded from The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression databases. Correlation analysis was used to evaluate the relationship between Rab11A expression and immune characteristics. Potential pathways were identified using the Kyoto Encyclopedia of Genes and Genomes and Gene Ontology analysis. Immunohistochemical analysis, colony formation assay, bromodeoxyuridine incorporation assay, immunofluorescence, and Western blot were used to explore potential function and mechanism. Analysis of the TCGA database showed significant upregulation of Rab11A expression in a variety of cancers. Rab11A was up-regulated in 82.4% of BRCA. High Rab11A expression is associated with poor survival in cancer patients and is a predictor of poor prognosis. CIBERSORT analysis showed that Rab11A was negatively associated with almost all immune cycle activity scores pan-cancer. The results of the TCGA-BRCA cohort were further confirmed by using pathological samples from clinical BRCA patients. The results showed that Rab11A expression was correlated with estrogen receptor (ER) and progesterone receptor expression in BRCA (p<0.05). Knockdown and overexpression of Rab11A affected the proliferation of BRCA cells. Further mechanistic studies revealed that down-regulation of ER alpha (ERα) and up-regulation of ER beta (ERβ) mediated Rab11A-induced inhibition of BRCA cell proliferation. Rab11A expression in pan-cancer is associated with poor prognosis and immune profile. In particular, in BRCA, Rab11A expression regulates cell proliferation by targeting ERα and ERβ. High Rab11A expression is tightly associated with immune characteristics, tumor microenvironment, and genetic mutations. These results provide a reference for exploring the role of Rab11A in pan-cancer and provide a new perspective for revealing potential therapeutic targets in BRCA.

Benign polymorphisms in the BRCA genes with linkage disequilibrium is associated with cancer characteristics.

Germline pathogenic mutation of the BRCA gene increases the prevalence of breast cancer. Reports on the benign variants of BRCA genes are limited. However, the definition of these variants might be altered with the accumulation of clinical evidence. Therefore, in the present study, we focused on benign single nucleotide polymorphisms (SNPs) of BRCA genes. Linkage disequilibrium was calculated from whole genome sequencing of the BRCA genes obtained from 500 healthy controls and 49 breast cancer patients. Sanger sequencing was used to confirm the mutation. The linkage disequilibrium was noted for seven and three SNPs in the BRCA1 and BRCA2 genes, respectively. Breast cancer with BRCA1/2 linkage disequilibrium was not correlated with a personal history of benign diseases or family history of cancer. Nevertheless, breast cancer with BRCA1 linkage disequilibrium was correlated with high tumor-infiltrating lymphocytes and positive extensive intraductal components. The patients with BRCA1 linkage disequilibrium tended to have worse disease-specific survival. Cancers with BRCA2 linkage disequilibrium are associated with a lower ratio of grade III cancer. Moreover, patients with BRCA2 linkage disequilibrium tended to have better overall survival. In conclusion, linkage disequilibrium from benign SNPs of the BRCA genes potentially affects cancer characteristics.

Application of CRISPR/Cas9 gene-editing technology in Alzheimers disease

Alzheimer's disease (AD) is a prevalent neurodegenerative disorder. It triggers metabolic disorders within the body due to genetic mutations, thus leading to irreversible damage to one's memory and brain. The primary pathogenic features of AD are intracellular neurofibrillary tangles caused by hyperphosphorylated Tau and extracellular amyloid plaques created by the buildup of -amyloid -protein (A). However, up to now, there has been no effective treatment program for Alzheimer's disease. And after a long time of development, many gene editing technologies have been perfected and utilized in practice. Among them, CRISPR-Cas9 technology is the most efficient and practical. As a result, an increasing number of scientists have examined and debated the potential use of CRISPR-Cas9 technology in the management of Alzheimer's disease. This review addresses the use of the CRISPR/Cas9 system to treat Alzheimer's disease and presents the disease's pathophysiology, including the establishment of AD models, genetic screening for the cause of AD, and targeted therapy for AD.

Prognostic impact of next-generation sequencing on myelodysplastic syndrome: A single-center experience.

Myelodysplastic syndromes (MDS) are clinically heterogeneous disorders characterized by peripheral blood cytopenias, poor differentiation, clonal hematopoiesis, and increased risk of developing acute myeloid leukemia (AML). While somatic mutations do not currently feature in prognostic scoring systems, they may impact the clinical phenotype. In recent years, next-generation sequencing (NGS) has enabled the opportunity to identify an increasing number of genetic abnormalities, including recurrent modifications in the TP53, DNMT3A, NRAS, NPM1, RUNX1, and FLT3 genes. Bone marrow aspirate samples of 56 patients with MDS were investigated for mutations using NGS. We compared the relationship between gene mutation status and laboratory characteristics, such as certain cytopenias, the revised international prognostic scoring system, MDS subtypes, karyotypes, AML development, and overall survival. Twenty-one genes were found to have gene mutations, including ASXL1, TET2, SRSF2, EZH2, CSF3R, NRAS, ETV6, SETBP1, RUNX1, DDX41, U2AF1, JAK2, FLT3ITD, SF3B1, DNAMT3A, PHF6, TP53, CEBPA, CBL, IDH2, and GATA2. At least one point mutation occurred in 64.2% of all patients, including 58.3% of those with normal cytogenetics. Thrombocytopenia (P = .016), anemia (P = .018), decreased overall survival (P = .017), and increased AML transformation (P = .023) have been revealed to be linked to non-SF3B1 mutations. MDS are frequently associated with somatic point mutations. According to early findings, NGS panels are extremely effective instruments that provide an entirely new viewpoint on the disease for particular individuals. Future prognostications will depend more on NGS because those who exhibit normal cytogenetics may additionally have gene mutations.

A Chinese CADASIL family with a rare heterozygous mutation in exon 2 of NOTCH3: A case report.

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is an inherited cerebrovascular disease caused by the neurogenic locus notch homolog protein 3 (NOTCH3) gene mutation. In recent years, most of the newly reported mutations of CADASIL patients mainly occur in exon 3 to 24, while the cases related to exon 2 mutation are rare, and clinical research data are relatively insufficient. In this study, we have reported a case of a rare heterozygous mutation c.128G>A (p.Cys43Tyr) in exon 2 of NOTCH3 in a 41-year-old Chinese man in the light of relevant literatures. A 41-year-old man who suffered slurred speech for 5 days and right lower limb weakness for 4 days was admitted to our hospital. Magnetic resonance imaging of the head revealed diffuse white matter lesions involving the outer capsular area and bilateral temporal poles. The rare heterozygous mutation c.128G>A (p.Cys43Tyr) in exon 2 of NOTCH3 was identified through molecular genetic testing. The proband was diagnosed as having CADASIL. Meanwhile, the same mutation was detected in 2 other family members III5 and IV9. Atorvastatin calcium tablet (20 mg qd) and aspirin enteric-coated tablet (100 mg qd). The patient was hospitalized for 3 weeks and discharged after his symptoms improved. The heterozygous Cys43Tyr mutation in exon 2 of NOTCH3 is rare. Thus, our case report complements the rare mutation of exon 2 and offers additional clinical data for CADASIL patients.

FOXN3-AS1: A Candidate Prognostic Marker and Epigenetic Target with Immunotherapeutic Implications in Acute Myeloid Leukemia.

We focused on the FOXN3 gene and selected its antisense transcripts (FOXN3-AS1) to investigate its potential involvement in acute myeloid leukemia (AML). Several integrated multi-omics datasets have expanded the horizons of the cancer landscape. With the emergence of new high-throughput technologies, a large number of non-coding RNAs have been confirmed to be involved in the pathogenesis of different types of hematological malignancies. We conducted experimental validation using quantitative polymerase chain reaction (qPCR) with bone marrow specimens from AML patients. Then, Kaplan-Meier (KM) and Receiver Operating Characteristic (ROC) curves were used to substantiate the prognostic association between FOXN3-AS1 and AML patients within the TCGA database. Correlation between FOXN3-AS1 expression and gene mutation, immune, and immune function using Spearman correlation analysis. To explore the physical and functional interaction between FOXN3-AS1 and the DNMT1 protein, we utilized the RPISeq web tool from Iowa State University. Subsequently, we performed qPCR experiments to test the effect of 5AzaC (DNMT1 inhibitor) on FOXN3-AS1 expression AML cell lines (THP1 and OCI-AML3). We leveraged the "OncoPredict" R package in conjunction with the Genomics of Drug Sensitivity (GDSC) database to predict drug response in AML patients expressing FOXN3-AS1. We observed a significant upregulation of FOXN3-AS1 expression in AML patients compared to healthy controls using clinical samples. The TCGA database revealed an association between high FOXN3-AS1 expression and adverse prognosis. In our subsequent analysis, genes with poor prognostic implications in AML patients were exclusively identified in the FOXN3-AS1 high-expression group, further corroborating this relationship. AML patients with higher FOXN3-AS1 expression levels may respond less optimally to immunotherapy than patients with lower levels. Besides, we computationally predicted the interaction of FOXN3- AS1 and DNMT1 protein and experimentally confirmed that DNMT1i (GSK-3484862) affects the expression level of FOXN3-AS1. We also found that the chemotherapy drugs (5-Fluorouralic, Cisplatin, Dactolisib, Sapitinib, Temozolomide, Ulixertinib, Vinorelbine, Ruxolitinib, Osimertinib and Cisplatin) showed favorable responses in AML patients with high FOXN3-AS1 expression levels. Our candidate approach identifies FOXN3-AS1 as a prognostic indicator of survival in AML with a potential immune-related role. The preliminary observations we made on FOXN3-AS1/DNMT1 crosstalk warrant more in-depth invested immunotherapeutic approaches in AML.

Skin metastasis of BRCA mutated prostate cancer: A case report and a brief review of literature.

Metastatic castration-resistant prostate cancer has a poor prognosis especially when harboring DNA damage repair gene mutations, nevertheless, in the case of pathogenic BRCA gene mutations, PARPi demonstrated a survival benefit and is a validated treatment. Nowadays, there is no data regarding unusual metastases after these drugs. Cutaneous metastases appear rarely in prostate cancer and were associated with a worse prognosis. Moreover, there are no consolidated data concerning skin tropism of prostate cancer cells, neither in the case of BRCA-associated cancers. Here, we report the case of a patient with a long history of BRCA1-mutated metastatic castration-resistant prostate cancer who developed a skin lesion on the scalp while on his fifth line of systemic therapy with olaparib. After a complete radical surgical excision, the pathology report showed prostate cancer localization. A diagnosis of skin metastasis from prostate cancer was reported. The patient then continued olaparib therapy; after 7 months from excision, he experienced further bone and biochemical progression but not cutaneous progression. A literature review of all reported cases of cutaneous metastasis in prostate cancer was conducted to shed light on the incidence, clinical presentation, diagnosis, treatment, and prognosis of this entity. We also reviewed published cases of skin metastasis in BRCA-associated cancers with an effort to correlate skin involvement with PARPi treatment, BRCAness status, and prognosis.

Comparison of Truenat Mycobacterium tuberculosis with line probe assay for the diagnosis of rifampicin resistance and mutation pattern of Mycobacterium tuberculosis

Abstract Background: There is an increasing incidence of multidrug-resistant tuberculosis (TB)/preextensively drug-resistant TB (XDR TB) and XDR TB globally. Therefore, rapid diagnostic tests with good sensitivity and specificity are need of hour. Truenat Mycobacterium tuberculosis (MTB) is one such test which gives results in 1–2 h and can withstand a variety of environmental conditions. Objective: The objective of this study was to compare Truenat MTB with line probe assay (LPA) for the diagnosis of rifampicin resistance and to study the mutation pattern of MTB. Materials and Methods: A comparative record-based study was carried out among 325 patients with multidrug-resistant TB. Sputum samples for pulmonary TB and appropriate site samples for extrapulmonary TB were obtained and tested with Truenat-MTB and LPA. A comparison between results obtained by Truenat-MTB and LPA was done. Based on first-line-LPA and second-line-LPA, gene mutation pattern was studied. Results: Males (69.2%) were more than females (30.8%). 30–49 (34.5%) years of age were most commonly affected. The sensitivity, specificity, positive predictive value, and negative predictive value of Truenat MTB compared to LPA were 82.86%, 93.45%, 60.41%, and 97.83%, respectively. The most common gene mutation observed was katG MUT1 in 59 cases. This was followed by rpoB MUT1 in three cases, rpoB MUT2A in two cases, rpoB MUT2B in four cases, and rpoB MUT3 in 12 cases. gyrA mutation was seen in nine cases among which gyrA MUT3A was seen in one case, gyrA MUT3B in one case, and gyrA MUT3C was seen in four cases. Two cases of rrs MUT1 were seen. Five cases of inhA MUT1 were seen. Conclusion: Truenat has been found to be economical, less time-consuming, giving fast results, and accurate in the diagnosis of DR-TB. The most common gene mutation observed was katG MUT1 in 59 cases.