Differences and similarities of GTF2I mutated thymomas in different Eurasian ethnic groups.
Ontology highlight
ABSTRACT:
SUBMITTER: Lang M
PROVIDER: S-EPMC10579828 | biostudies-literature | 2023 Sep
REPOSITORIES: biostudies-literature
Publications
Differences and similarities of <i>GTF2I</i> mutated thymomas in different Eurasian ethnic groups.
Lang Matthias M Kazdal Daniel D Mohr Isabelle I Anamaterou Chrysanthi C
Translational lung cancer research 20230922 9
Similar Datasets
Project description:Thymomas are the most frequent adult mediastinal cancers. Their etiology is unknown and their pathogenesis poorly understood. Racial, ethnic and environmental factors influence tumorigenesis in many cancers, but their role in thymomas remains unclear to date. In this study that included pretreatment thymoma cases from India and Germany (n = 37 and n = 77, respectively) we compared i) the prevalence of the thymoma-specific chromosome 7 c.74146970T > A mutation of the GTF2I gene in type A and AB thymomas; ii) epidemiological features; and iii) the frequency of myasthenia gravis (MG). Due to a known predominance of GTF2I mutation in A and AB histotypes, we included only a marginal number of type B thymomas as a control group in both cohorts. While the distribution of histological types between the cohorts was similar (p = 0.1622), Indian patients were strikingly younger (p < 0.0001; median age 50 vs. 65 years) and showed significantly lower tumour stage (Masaoka-Koga stage I) at primary diagnosis (p = 0.0005) than the German patients. In patients with known MG status (n = 17 in Indian and n = 25 in German cohort), a clear trend towards more frequent MG was observed in the Indian group (p = 0.0504; 48 vs. 82%). The prevalence of the GTF2I mutation (analysed in n = 34 Indian and n = 77 German patients) was identical in the two cohorts. We conclude that racial-ethnic and environmental factors do not significantly influence the most common molecular feature of thymomas but may have an impact on the timing of clinical presentation.
| S-EPMC8419886 | biostudies-literature
Project description:Thymomas are rare mediastinal tumors that are difficult to treat and pose a major public health concern. Identifying mutations in target genes is vital for the development of novel therapeutic strategies. Type A thymomas possess a missense mutation in GTF2I (chromosome 7 c.74146970T>A) with high frequency. However, the molecular pathways underlying the tumorigenesis of other thymomas remain to be elucidated. We aimed to detect this missense mutation in GTF2I in other thymoma subtypes (types B). This study involved 22 patients who underwent surgery for thymomas between January 2014 and August 2019. We isolated tumor cells from formalin-fixed paraffin-embedded tissues from the primary lesions using laser-capture microdissection. Subsequently, we performed targeted sequencing to detect mutant GTF2I coupled with molecular barcoding. We used PyClone analysis to determine the fraction of tumor cells harboring mutant GTF2I. We detected the missense mutation (chromosome 7 c.74146970T>A) in GTF2I in 14 thymomas among the 22 samples (64%). This mutation was harbored in many type B thymomas as well as type A and AB thymomas. The allele fraction for the tumors containing the mutations was variable, primarily owing to the coexistence of normal lymphocytes in the tumors, especially in type B thymomas. PyClone analysis revealed a high cellular prevalence of mutant GTF2I in tumor cells. Mutant GTF2I was not detected in other carcinomas (lung, gastric, colorectal, or hepatocellular carcinoma) or lymphomas. In conclusion, the majority of thymomas harbor mutations in GTF2I that can be potentially used as a novel therapeutic target in patients with thymomas.
| S-EPMC7466068 | biostudies-literature
Project description:BackgroundMany differences between different ethnic groups have been observed, such as skin color, eye color, height, susceptibility to some diseases, and response to certain drugs. However, the genetic bases of such differences have been under-investigated. Since the HapMap project, large-scale genotype data from Caucasian, African and Asian population samples have been available. The project found that these populations were located in different areas of the PCA (Principal Component Analysis) plot. However, as an unsupervised method, PCA does not measure the differences in each single nucleotide polymorphism (SNP) among populations.ResultsWe applied an advanced mutual information-based feature selection method to detect associations between SNP status and ethnic groups using the latest HapMap Phase 3 release version 3, which included more sub-populations. A total of 299 SNPs were identified, and they can accurately predicted the ethnicity of all HapMap populations. The 10-fold cross validation accuracy of the SMO (sequential minimal optimization) model on training dataset was 0.901, and the accuracy on independent test dataset was 0.895.ConclusionsIn-depth functional analysis of these SNPs and their nearby genes revealed the genetic bases of skin and eye color differences among populations.
| S-EPMC4687076 | biostudies-literature
Project description:AbstractTo determine the differences in intestinal flora between Uygur and Han patients with ulcerative colitis (UC).Microbial diversity and structural composition of fecal bacteria from patients with UC and their matched healthy spouses or first-degree relatives were analyzed using high-throughput sequencing technology.The fecal microbial diversity and abundance index of Uygur patients with UC (UUC) were significantly lower compared with the Uygur normal control group, while there was no significant difference between the Han UC patients (HUC) and the Han normal control group (HN). Compared with their respective control groups, Uygur UC patients and Han UC patients had a different main composition of human intestinal flora (P < .05). The abundance of Burkholderia, Caballeronia, Paraburkholderia in the UUC group were higher compared with the HUC group, while Faecalibacterium, Bifidobacterium, and Blautia in the HUC group were higher than those in the UUC group (P < .05). Veillonella in the UUC group was higher than that in the Uygur normal control group group, while Subdoligranulum and Ruminococcaceae_UCG-002 were significantly lower (P < .05). Prevotella_9 in the HUC group was significantly higher than that in HN group, while Blautia, Anaerostipes, and [Eubacterium]_hallii_group were significantly lower. Moreover, the top 6 species in order of importance were Christensenellaceae_R_7_group, Ruminococcae_ucg_005, Ruminococcae_ucg_010, Ruminococcae_ucg_013, Haemophilus, and Ezakiella.The difference in intestinal microflora structure may be one of the reasons for the clinical heterogeneity between Uygur and Han patients with UC. Christensenellaceae_R_7_group, Ruminococcae_ucg_005, Ruminococcae_ucg_010, Ruminococcae_ucg_013, Haemophilus, and Ezakiella could be used as potential biomarkers for predicting UC.
| S-EPMC8360419 | biostudies-literature
Project description:Macropinocytosis is a unique pathway of endocytosis characterised by the nonspecific internalisation of large amounts of extracellular fluid, solutes and membrane in large endocytic vesicles known as macropinosomes. Macropinocytosis is important in a range of physiological processes, including antigen presentation, nutrient sensing, recycling of plasma proteins, migration and signalling. It has become apparent in recent years from the study of specialised cells that there are multiple pathways of macropinocytosis utilised by different cell types, and some of these pathways are triggered by different stimuli. Understanding the physiological function of macropinocytosis requires knowledge of the regulation and fate of the macropinocytosis pathways in a range of cell types. Here, we compare the mechanisms of macropinocytosis in different primary and immortalised cells, identify the gaps in knowledge in the field and discuss the potential approaches to analyse the function of macropinocytosis in vivo.
| S-EPMC7463864 | biostudies-literature
Project description:Atopic dermatitis (AD) is a common chronic inflammatory skin disease with a high prevalence worldwide, including countries from Asia, Africa, and Latin America, and in different ethnic groups. In recent years, more attention has been placed on the heterogeneity of AD associated with multiple factors, including a patient's ethnic background, resulting in an increasing body of clinical, genetic, epidemiologic, and immune-phenotypic evidence that delineates differences in AD among racial groups. Filaggrin (FLG) mutations, the strongest genetic risk factor for the development of AD, are detected in up to 50% of European and 27% of Asian AD patients, but very rarely in Africans. Th2 hyperactivation is a common attribute of all ethnic groups, though the Asian endotype of AD is also characterized by an increased Th17-mediated signal, whereas African Americans show a strong Th2/Th22 signature and an absence of Th1/Th17 skewing. In addition, the ethnic heterogeneity of AD may hold important therapeutic implications as a patient's genetic predisposition may affect treatment response and, thereby, a tailored strategy that better targets the dominant immunologic pathways in each ethnic subgroup may be envisaged. Nevertheless, white patients with AD represent the largest ethnicity enrolled and tested in clinical trials and the most treated in a real-world setting, limiting investigations about safety and efficacy across different ethnicities. The purpose of this review is to describe the heterogeneity in the pathophysiology of AD across ethnicities and its potential therapeutic implications.
| S-EPMC10095524 | biostudies-literature
Project description: Not available
| S-EPMC11250226 | biostudies-literature
Project description: Not available
| S-EPMC10716055 | biostudies-literature
Project description:BACKGROUND: Spinal muscular atrophy (SMA) is the most common inherited lethal disease of children. Various genetic deletions involving the bi-allelic loss of SMN1 exon 7 are reported to account for 94% of affected individuals. Published literature places the carrier frequency for SMN1 mutations between 1 in 25 and 1 in 50 in the general population. Although SMA is considered to be a pan-ethnic disease, carrier frequencies for many ethnicities, including most ethnic groups in North America, are unknown. OBJECTIVES AND METHODS: To provide an accurate assessment of SMN1 mutation carrier frequencies in African American, Ashkenazi Jewish, Asian, Caucasian, and Hispanic populations, more than 1000 specimens in each ethnic group were tested using a clinically validated, quantitative real-time polymerase chain reaction (PCR) assay that measures exon 7 copy number. RESULTS: The observed one-copy genotype frequency was 1 in 37 (2.7%) in Caucasian, 1 in 46 (2.2%) in Ashkenazi Jew, 1 in 56 (1.8%) in Asian, 1 in 91 (1.1%) in African American, and 1 in 125 (0.8%) in Hispanic specimens. Additionally, an unusually high frequency of alleles with multiple copies of SMN1 was identified in the African American group (27% compared to 3.3-8.1%). This latter finding has clinical implications for providing accurate adjusted genetic risk assessments to the African American population. CONCLUSIONS: Differences in the frequency of SMA carriers were significant among several ethnic groups. This study provides an accurate assessment of allele frequencies and estimates of adjusted genetic risk that were previously unavailable to clinicians and patients considering testing.
| S-EPMC2729371 | biostudies-literature
Project description:BackgroundInter-ethnic differences have been reported for many mental health outcomes in the UK, but no systematic review on child mental health has been published. The aim of this review is to compare the population-based prevalence of child mental disorders between ethnic groups in Britain, and relate these findings to ethnic differences in mental health service use.MethodsA systematic search of bibliographic databases for population-based and clinic-based studies of children aged 0-19, including all ethnic groups and the main child mental disorders. We synthesised findings by comparing each minority group to the White British study sample.Results31 population-based and 18 clinic-based studies met the inclusion criteria. Children in the main minority groups have similar or better mental health than White British children for common disorders, but may have higher rates for some less common conditions. The causes of these differences are unclear. There may be unmet need for services among Pakistani and Bangladeshi children.ConclusionInter-ethnic differences exist but are largely unexplained. Future studies should address the challenges of cross-cultural psychiatry and investigate reasons for inter-ethnic differences.
| S-EPMC2515844 | biostudies-literature