Genetic testing and molecular biomarkers最新文献

{"title":"Immune Regulatory Circular RNAs, circRasGEF1B and circHIPK3, are Upregulated in Peripheral Blood Mononuclear Cells of COVID-19 Patients.","authors":"Ebrahim Mirzaei, Abbas Shahi, Abdolreza Daraei, Bahram Movahedi, Jalal Karimi, Mojtaba Farjam, Yosef Gholampoor, Mohammad Hassan Meshkibaf, Amir Ansari, Zahra Firoozi, Yaser Mansoori","doi":"10.1089/gtmb.2024.0337","DOIUrl":"10.1089/gtmb.2024.0337","url":null,"abstract":"<p><p><b><i>Background:</i></b> COVID-19 is one of the worst pandemics worldwide, and its diagnosis and treatment are of great importance. Recent evidence has shown that circular RNA (circRNA deregulation is involved in different infectious diseases. In the present study, we tried to investigate the expression of cirRNAs RasGEF1B (hsa_circ_0127052), HIPK3 (hsa_circ_100783), and GATAD2A (hsa_circ_0050236) in COVID-19 patients. <b><i>Methods:</i></b> Using quantitative real-time polymerase chain reaction, the expression profiles of candidate circRNAs were detected in 57 COVID-19 patients and 51 healthy controls. As part of the process of identifying a candidate circRNA that is sensitive and specific, receiver operating characteristic (ROC) curves were also utilized. <b><i>Results:</i></b> Our results showed higher expression levels of circRasGEF1B and circHIPK3 in COVID-19 patients, however, circGATAD2A showed no statistical difference between patients and controls. ROC curves showed that circRasGEF1B (hsa_circ_0127052), and HIPK3 (hsa_circ_100783) had favorable specificity and sensitivity, whereas GATAD2A (hsa_circ_0050236) did not. <b><i>Conclusion:</i></b> In summary, our study highlights the potential of CircRasGEF1B (hsa_circ_0127052) and HIPK3 (hsa_circ_100783) as biomarkers for COVID-19 diagnosis due to their high expression levels and demonstrated diagnostic accuracy. These findings suggest that circRNAs could play a crucial role in the development of diagnostic tools for COVID-19, providing a new avenue for early detection and management of the disease.</p>","PeriodicalId":12603,"journal":{"name":"Genetic testing and molecular biomarkers","volume":" ","pages":"452-459"},"PeriodicalIF":1.1,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142581676","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Differential Analysis of Pathogenic Variants in Thoracic Aortic Aneurysm and Dissection at Different Ages.","authors":"Shilei Luo, Fei Leng, He Zhao, Wei Li, Qiaochu Wang, Jun Guo","doi":"10.1089/gtmb.2024.0139","DOIUrl":"10.1089/gtmb.2024.0139","url":null,"abstract":"<p><p><b><i>Objective:</i></b> To identify genetic variants associated with Stanford A thoracic aortic aneurysm and dissection (ATAAD) using whole-exome sequencing (WES) and analyze positive mutation rates among patients of different onset ages. <b><i>Methods:</i></b> WES was performed on 62 sporadic Chinese ATAAD patients (51-74 years old), and then grouped based on onset age together with 73 previously reported TAAD patients (19-50 years old): ≤35, 36-45, 46-55, and >55 years. The proportion of patients with pathogenic/likely pathogenic (P/LP) variants in TAAD causal genes was compared across groups. <b><i>Results:</i></b> The average onset age of the 62 patients was 57.66 years. Eight P/LP variants were identified (two novel, six previously described) in five known TAAD causal genes (<i>FBN1</i>, <i>SMAD3</i>, <i>TGFBR2</i>, <i>TGFB2</i>, and <i>MYLK</i>) in eight individuals. P/LP variant positive rates among patients across age groups were: 22.73% for ≤35 years, 32% for 36-45 years, 15.52% for 46-55 years, and 3.33% for >55 years. Significant differences (<i>p</i> = 0.0077) were observed between 36-45 and >55 years group. <b><i>Conclusions:</i></b> ATAAD patients aged 36-45 years old at diagnosis had a higher chance of having a P/LP variant and patients >55 years old had the lowest P/LP diagnostic rate. Therefore, gene screening in ATAAD patients ≤55 years old is key to improved diagnostic rate.</p>","PeriodicalId":12603,"journal":{"name":"Genetic testing and molecular biomarkers","volume":"28 11","pages":"431-437"},"PeriodicalIF":1.1,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142638681","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association of ANRIL Gene Polymorphisms with Gastric Cancer Risk: A Case-Control Study.","authors":"Samaneh Hasani, Farhad Pourfarzi, Mohammad Mazani, Abbas Yazdanbod, Aliakbar Fazaeli","doi":"10.1089/gtmb.2024.0302","DOIUrl":"10.1089/gtmb.2024.0302","url":null,"abstract":"<p><p><b><i>Background:</i></b> Gastric cancer's (GC) cause is unknown, but its complexity indicates that, in addition to environmental factors, it may have genetic origins. Scientists are studying single-nucleotide polymorphisms (SNPs) in the antisense noncoding RNA in the INK4 locus (ANRIL) gene, which encodes a long noncoding RNA molecule. They found a link between the ANRIL gene product and some polymorphisms and GC, suggesting genetic changes may lead to precancerous conditions. <b><i>Methods:</i></b> In a case-control research that included 250 patients with GC and 210 controls who were age- and gender-matched, four SNPs within the ANRIL gene were genotyped. These SNPs were rs1333049, rs496892, rs2383207, and rs2151280. Tetra-primer amplification refractory mutation system-PCR was utilized to carry out the process of genotyping. <b><i>Results:</i></b> It was found that the chance of developing GC was connected with three SNPs rs2151280, rs1333049, and rs496892. Nevertheless, rs2383207 did not demonstrate any meaningful connection. In addition, whereas CCTC and TTCC haplotypes were shown to be less common, certain haplotypes that contained these SNPs (TTCG, TCTC, and TTTC) displayed a considerably higher prevalence in the cancer group in comparison to the control group. <b><i>Conclusion:</i></b> This study showed novel associations between specific ANRIL gene polymorphisms (SNPs) and the risk of GC. These findings shed light on the potential role of ANRIL SNPs in GC risk and highlight the need for additional research to clarify the underlying functional processes. Understanding these functional processes might lead to developing novel diagnostic or treatment approaches for this cancer.</p>","PeriodicalId":12603,"journal":{"name":"Genetic testing and molecular biomarkers","volume":" ","pages":"445-451"},"PeriodicalIF":16.4,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142389695","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evaluation of Multigene Methylation for Blood-Based Detection of Colorectal Cancer.","authors":"Yingshuo Xu, Ailin Tan, Rui Liang, Huaidong Qu, Xiankun Li, Zhiqiang Wang","doi":"10.1089/gtmb.2023.0754","DOIUrl":"10.1089/gtmb.2023.0754","url":null,"abstract":"<p><p><b><i>Background:</i></b> Early screening for colorectal cancer (CRC) has the potential to improve patient prognosis, but current screening methods are limited. In this prospective study, we aimed to evaluate the multigene (<i>Septin9, SDC2, KCNQ5,</i> and <i>IKZF1</i>) detection in patient plasma for CRC diagnosis. <b><i>Methods:</i></b> Overall, 67 participants were enrolled, including 31 patients with CRC, 17 patients with colorectal polyp, and 19 normal controls who underwent colonoscopy. Carcinoembryonic antigen (CEA) and <i>Septin9, SDC2, KCNQ5</i>, and <i>IKZF1</i> methylation tests were performed. Sensitivity, specificity, and the area under the receiver operating characteristic (ROC) curve were used to evaluate the diagnostic value of each biomarker. The association between positive rates of methylated <i>Septin9, SDC2, KCNQ5</i>, and <i>IKZF1</i> and the clinicopathological characteristics of CRC was also analyzed. <b><i>Results:</i></b> The positive rate of multigene methylation detection was 87.1% (27/31) in patients with CRC, which was higher than single indicators: CEA (51.61%, 16/31), <i>Septin9</i> (41.94%, 13/31), <i>SDC2</i> (41.94%, 13/31), <i>KCNQ5</i> (58.06%, 18/31), and <i>IKZF1</i> (32.26%, 10/31). In the colorectal polyp group, the rate of multigene methylation detection is 88.24% (15/17), which was also higher than single indicator: CEA (17.65%, 3/17), <i>Septin9</i> (11.76%, 2/17), <i>SDC2</i> (64.71%, 11/17), <i>KCNQ5</i> (58.82%, 10/17), and <i>IKZF1</i> (35.29%, 6/17). The ROC curves further showed better diagnostic value of the multigene test for CRC than any single gene. Correlation analysis found that the positive rate of the test was not affected by patients' clinicopathologic characteristics. <b><i>Conclusion:</i></b> The combination of methylated <i>Septin9, SDC2, KCNQ5</i>, and <i>IKZF1</i> tests is preferable to individual gene tests for patients with CRC and polyp.</p>","PeriodicalId":12603,"journal":{"name":"Genetic testing and molecular biomarkers","volume":" ","pages":"402-409"},"PeriodicalIF":1.1,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142283951","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Human Leukocyte Antigen-G Gene Polymorphism in Peninsular Malaysia: A Preliminary Report.","authors":"Che Ghazali Norul Hajar, Zulkafli Zefarina, Nor Suhaila Md Riffin, Tuan Hulwani Tuan Mohammad, Mohd Nazri Hassan, Sharifah-Nany Rahayu-Karmilla Syed-Hassan, Mohd Yusmaidie Aziz, Abd Rashid Nur Haslindawaty, Geoffrey Keith Chambers, Hisham Atan Edinur","doi":"10.1089/gtmb.2023.0492","DOIUrl":"10.1089/gtmb.2023.0492","url":null,"abstract":"<p><p><b><i>Introduction:</i></b> Expression of the nonclassical human leukocyte antigen (<i>HLA</i>)<i>-G</i> gene is upregulated in placenta during pregnancy. In other cells, HLA-G is upregulated during parasitic infections and allergic reactions. Polymorphism at the <i>HLA-G</i> gene locus has been reported for many populations, but so far not for any ethnic groups in Malaysia. In this survey, we screened for genetic variation in <i>HLA-G</i> genes from representative Malay, Chinese, and Indian individuals living in Peninsular Malaysia. <b><i>Materials and Methods:</i></b> Blood samples were obtained with informed consent, and ethnicity classes were assigned based on self-declared pedigree information. Exons 2, 3, and 4 of the <i>HLA-G</i> gene were amplified by polymerase chain reaction and subjected to Sanger sequencing. <b><i>Results:</i></b> The most common genotype in Malays and Indians was found to be <i>HLA-G*01:01:01:01/01:01:01:01</i> with frequencies of 0.206 and 0.167, respectively, whereas the <i>HLA-G*01:01:03:01/01:01:01:01</i> genotype was the one most frequently observed in Chinese (0.221). Based on this study, <i>HLA-G*01:01:01:01</i> (0.427-0.448) is the most frequent <i>HLA-G</i> allele in the all three ethnic groups. In contrast, <i>HLA-G*01:01:02:01</i> (0.186) was observed as the second most frequent <i>HLA-G</i> allele in Malays and <i>HLA-G*01:04:01</i> in Chinese and Indians, (0.188-0.198, respectively). Several minor <i>HLA-G</i> alleles were detected at low frequency in Malays, Chinese, or Indians (<i>HLA-G*01:01:05</i>, <i>01:01:09</i>, <i>01:04:02</i>, and <i>01:04:03</i>). These have only rarely, if ever, been reported in other population groups. Subsequent statistical analysis including using principal coordinate data mapping showed the Malays, Chinese, and Indians are distinct but quite closely related to one another as compared with other population groups from across Europe and Africa. <b><i>Conclusion:</i></b> The HLA-G population data collected in this study showed that the ancestrally unrelated Malays, Chinese, and Indians are genetically distinct. This new database provides a foundation for further studies to capture <i>HLA-G</i> allelic diversity in uncharacterized populations of Malaysia and for future attempts to identify their roles in disease resistance and susceptibility.</p>","PeriodicalId":12603,"journal":{"name":"Genetic testing and molecular biomarkers","volume":" ","pages":"393-401"},"PeriodicalIF":1.1,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142283952","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Whole-Genome Sequencing of Newly Emerged Fungal Pathogen <i>Aspergillus Lentulus</i> and Its Azole Resistance Gene Prediction.","authors":"Xiaodong Wang, Aikedai Yusufu, Hadiliya Hasimu, Paride Abliz","doi":"10.1089/gtmb.2024.0002","DOIUrl":"https://doi.org/10.1089/gtmb.2024.0002","url":null,"abstract":"&lt;p&gt;&lt;p&gt;&lt;b&gt;&lt;i&gt;Aims:&lt;/i&gt;&lt;/b&gt; &lt;i&gt;Aspergillus lentulus&lt;/i&gt; is an important newly recorded species in the &lt;i&gt;A. fumigatus&lt;/i&gt; complex and its resistance to azole drugs and the high mortality rate of infected individuals have emerged as problems. Comprehensive understanding of the &lt;i&gt;A. lentulus&lt;/i&gt; is limited due to lack of genome-wide fine mapping data. The aim of this study was to investigate the &lt;i&gt;A. lentulus&lt;/i&gt; signature at the molecular level, analyze the genome-wide profile of this strain, and predict its possible genes that execute azole resistance. &lt;b&gt;&lt;i&gt;Methods:&lt;/i&gt;&lt;/b&gt; In this study, a whole-genome sequencing of a clinically isolated &lt;i&gt;A. lentulus&lt;/i&gt; strain (named &lt;i&gt;A. lentulus&lt;/i&gt; PWCAL1) was studied by PacBio Sequel sequencing platform. Azole resistance genes were predicted based on whole-genome sequencing data analysis, gene function annotation, comparative genomic analysis, and BLASTP alignment using the Mycology Antifungal Resistance Database to comprehensively understanding the genome-wide features, pathogenicity, and resistance mechanisms of &lt;i&gt;A. lentulus&lt;/i&gt;. &lt;b&gt;&lt;i&gt;Results:&lt;/i&gt;&lt;/b&gt; The results of whole-genome sequencing demonstrated that the total length of &lt;i&gt;A. lentulus&lt;/i&gt; PWCAL1 genome was 31255105 bp, the GC content was 49.24%, and 6883 coding genes were predicted. A total of 4565, 1824, and 6405 genes were annotated in the Gene Ontology, Clusters of Orthologous Groups, and Kyoto Encyclopedia of Genes and Genomes databases, respectively. In the Pathogen Host Interactions Database and the Database of Fungal Virulence Factors, 949 and 259 interacting virulence factors were identified, respectively, with the main virulence factor-mutant virulence phenotype, being enriched in reduced virulence. Comparative genomic analysis showed that there were 5456 consensus core genes in this strain and four closely related strains of &lt;i&gt;A. fumigatus&lt;/i&gt; complex, which were mainly involved in human diseases, metabolism, organismal systems, etc. Among the three aligned &lt;i&gt;A. lentulus&lt;/i&gt; strains, the number of unique genes of this bacterium was the highest with a number of 171, and these genes were mainly associated with carbohydrate metabolism and cell growth and death. Resistance gene prediction demonstrated that the A5653 gene of this bacterium had &lt;i&gt;F46Y/N248T&lt;/i&gt; double point mutations on the &lt;i&gt;CYP51A&lt;/i&gt; gene, but no tandem repeat mutations in the promoter region were detected. Furthermore, 12 genes belonging to the fungal multidrug resistance ATP-binding cassette (ABC) transporters were identified based on the complete genome sequence and phylogenetic analysis of A. lentulus, which belonged to the ALDp subfamily, the PDR subfamily (&lt;i&gt;AtrB&lt;/i&gt;, &lt;i&gt;CDR1&lt;/i&gt;, and &lt;i&gt;CDR2&lt;/i&gt;), and the MDR subfamily (&lt;i&gt;MDR1&lt;/i&gt;), respectively, and there were four genes that are annotated to the major facilitator superfamily multidrug transporter. Further phylogenetic tree classification of the ABC transporter subfamilies predicted in the nine selected ","PeriodicalId":12603,"journal":{"name":"Genetic testing and molecular biomarkers","volume":"28 10","pages":"410-430"},"PeriodicalIF":1.1,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142462817","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Analysis of <i>ANO6, HAPLN1</i>, and <i>EDIL3</i> Polymorphisms in Patients with Ankylosing Spondylitis in a Chinese Han Population: A Case-Control Study.","authors":"Zijian Lian, Wei Luo, Jun Liu, Jing Wang, Wei Chai, Yan Wang, Sahil Sethi, Xinlong Ma","doi":"10.1089/gtmb.2023.0569","DOIUrl":"10.1089/gtmb.2023.0569","url":null,"abstract":"<p><p><b><i>Background:</i></b> Earlier research has demonstrated a genetic basis for the susceptibility to ankylosing spondylitis (AS) and the severity of AS. By employing a genome-wide association study, recent work has established a correlation between the susceptibility to AS and the <i>ANO6, HAPLN,</i> and <i>EDIL3</i> genes in a Western study population-though alternative studies have not corroborated these findings. This study aims to examine the effects of <i>ANO6</i>, <i>HAPLN1</i>, and <i>EDIL3</i> polymorphisms on the susceptibility and severity of AS among the predominantly Chinese Han population. <b><i>Methods:</i></b> The study involved the collection of blood samples from 497 patients with AS and 498 nonrelated healthy individuals. All participants in the study were human leukocyte antigen (HLA) HLA-B27 positive and of Han Chinese descent. Illness severity was the criteria used for classifying patients with AS. Thirteen tagSNPs in <i>ANO6</i>, <i>HAPLN1</i>, and <i>EDIL3</i> were chosen and then subjected to genetic typing. Analysis was conducted on the occurrence rates of various genotypes and alleles between the control group and patients with varying AS severity. <b><i>Results:</i></b> Following Bonferroni correction, it was found that the rs4768085 and rs17095830 single nucleotide polymorphism (SNPs) in <i>ANO6</i> were related to the susceptibility to AS. Further, the rs6869296 SNP in <i>HAPLN1</i> and the rs2301071 SNP between <i>EDIL3</i> and <i>HAPLN1</i> were also related to AS susceptibility. Regarding AS severity, the rs4768085, rs2897868, rs7965430, and rs11182965 SNPs in <i>ANO6</i> were found to be associated. <b><i>Conclusions:</i></b> Among the Han population in China, the <i>ANO6 and HAPLN1</i> genes are related to the susceptibility to AS; the <i>ANO6</i> gene is also associated with the severity of AS.</p>","PeriodicalId":12603,"journal":{"name":"Genetic testing and molecular biomarkers","volume":" ","pages":"385-392"},"PeriodicalIF":1.1,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142365022","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Relationship Between IL-10 Single Nucleotide Polymorphisms (rs1800871, rs1800872, and rs1800896) and the Severity of COVID-19.","authors":"Hossein Azadinejad,Parisa Feizollahi,Alireza Rezaeimanesh,Farhad Salari,Ali Gorgin Karaji","doi":"10.1089/gtmb.2024.0276","DOIUrl":"https://doi.org/10.1089/gtmb.2024.0276","url":null,"abstract":"Background: Interleukin-10 (IL-10) is an anti-inflammatory cytokine whose levels are elevated in patients with severe COVID-19. IL-10 polymorphisms may play a role in increasing IL-10 levels and the severity of COVID-19. This study aimed to investigate the relationship between IL-10 single nucleotide polymorphisms (SNPs) (rs1800896 [-1082 C < T], rs1800871 [-819 A > G], and rs1800872 [-592 T > G]) and the severity of COVID-19 in patients from Kermanshah Province, Iran. Methods: A total of 150 patients with mild COVID-19 (84 men and 66 women aged 40.1 ± 12.44 years) and 143 patients with severe COVID-19 (76 men and 67 women aged 61.04 ± 15.65 years) participated in this study. Blood samples were collected from the patients, DNA was extracted, and the genotype of each SNPs was determined using the polymerase chain reaction-restriction fragment length polymorphism method. Result: The results of this study did not show a significant relationship between the genotypes of the three studied SNPs and the severity of COVID-19 (p > 0.05). Conclusion: According to our findings, these SNPs were not associated with COVID-19 severity in patients in Kermanshah.","PeriodicalId":12603,"journal":{"name":"Genetic testing and molecular biomarkers","volume":"10 1","pages":""},"PeriodicalIF":1.4,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142209334","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genomic Landscape of Osteosarcoma of Bone in an Older-Aged Patient Population and Analysis of Possible Etiologies Based on Molecular Signature.","authors":"Hatem Kaseb, Chichun Tan, Jeffrey P Townsend, Jose Costa, William B Laskin","doi":"10.1089/gtmb.2024.0080","DOIUrl":"10.1089/gtmb.2024.0080","url":null,"abstract":"<p><p><b><i>Background:</i></b> Osteosarcoma (OS), the most common primary malignant bone tumor, occurs mostly in the pediatric and adolescent (P/A) population where it has been subject to intense study whereas OS arising in the older-aged adult population has undergone less scrutiny. <b><i>Materials and Methods:</i></b> In this study, we assess the molecular aberrations detected in eight older adult patients (>59 years of age) with OS of bone by whole-exome sequencing (WES) on formalin-fixed, paraffin-embedded tissue and quantified the contributions of endogenous and exogenous mutational processes to tumor mutational burden and to tumorigenesis through computational analysis. <b><i>Results:</i></b> We identified 86 clinically significant somatic mutations. <i>TP53</i> mutations occurred in OSs of three patients and one patient harbored a pathogenic germline mutation of <i>TP53</i>. Loss-of-heterozygosity of DNA-damage repair genes occurred in all six tumors evaluated. Computational analysis of single nucleotide variants within each tumor detected eight distinct mutagenic processes of which age-associated mutational processes, thiopurine chemotherapy, and defective homologous DNA recombination repair contributed the most to both tumor mutation burden and tumor pathogenesis. <b><i>Conclusion:</i></b> The genomic landscape of our older OS patients deciphered by WES is extremely diverse with only 15% of mutated somatic genes uncovered in our study previously described in P/A-enriched OS studies. Endogenous age-related mutagenic processes, defective DNA homologous recombination repair, and exogenous effects of chemotherapy are mainly responsible for pathogenic mutations in OS occurring in our cohort.</p>","PeriodicalId":12603,"journal":{"name":"Genetic testing and molecular biomarkers","volume":" ","pages":"351-359"},"PeriodicalIF":1.1,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141758201","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Kawasaki Disease: An update on Genetics and Pathophysiology.","authors":"Evdoxia Sapountzi, Eleni P Kotanidou, Vasiliki-Rengina Tsinopoulou, Kallirhoe Kalinderi, Liana Fidani, Andreas Giannopoulos, Assimina Galli-Tsinopoulou","doi":"10.1089/gtmb.2024.0035","DOIUrl":"10.1089/gtmb.2024.0035","url":null,"abstract":"<p><p>Kawasaki disease (KD), a systemic vasculitic condition predominantly affecting children, remains a significant challenge in pediatric health care. First identified in 1967, KD is now recognized as the primary cause of pediatric ischemic heart disease in developed countries. This review provides a comprehensive update of KD, focusing on biomarkers, pathophysiology, and genetic associations. KD's clinical manifestation, including symptoms such as persistent fever and mucocutaneous changes, often overlaps with other pediatric conditions, complicating its diagnosis. This ambiguity, especially in cases of incomplete KD, highlights the critical need for specific biomarkers and more precise diagnostic methods. Recent studies have made promising advancements in identifying serum biomarkers and microRNAs, contributing to the development of rapid diagnostic tools. However, these are yet to be fully integrated into clinical practice. The article focuses on the pathophysiological aspects of KD, highlighting the potential for targeted therapies and personalized medicine approaches based on genetic predispositions. Collaborative efforts in global research and raising public awareness about KD are emphasized as key strategies for improving its management. This review presents the current understanding of KD while pointing out the gaps and future directions in research and clinical care. The ultimate goal is to enhance diagnostic accuracy, optimize treatment strategies, and improve patient outcomes, thereby addressing the complexities of this enigmatic and potentially life-threatening condition in pediatric medicine.</p>","PeriodicalId":12603,"journal":{"name":"Genetic testing and molecular biomarkers","volume":" ","pages":"373-383"},"PeriodicalIF":1.1,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142055378","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}