Cancer Genetics最新文献

{"title":"Contribution of ERCC2 rs13181 (Lys751Gln) and rs1799793 (Asp312Asn) polymorphisms to the risk of bladder cancer in Bangladesh","authors":"Md. Ariful Islam ,&nbsp;Saima Mubashshira ,&nbsp;Md. Mostafijur Rahman ,&nbsp;Yearul Kabir","doi":"10.1016/j.cancergen.2024.11.002","DOIUrl":"10.1016/j.cancergen.2024.11.002","url":null,"abstract":"<div><h3>Background</h3><div>Human Excision Repair Cross-Complementation Group 2 (ERCC2) proteins play a vital role in the nucleotide excision repair pathway through ATP-dependent helicase activity. Several studies found that polymorphisms in the ERCC2 gene are associated with susceptibility to different cancers, although the outcomes were confusing.</div></div><div><h3>Objective</h3><div>As a result, in this retrospective study, we investigated the relationship between genetic polymorphisms of the ERCC2 gene at codons 312 (rs1799793) and 751 (rs13181) and bladder cancer susceptibility in Bangladesh, as well as the disease's aggressiveness.</div></div><div><h3>Methods</h3><div>Genetic polymorphisms of ERCC2 were assayed by the polymerase chain reaction-based restriction fragment length polymorphism (PCR-RFLP) method with 121 bladder cancer patients and 130 healthy controls.</div></div><div><h3>Results</h3><div>Patients who had the Gln/Gln polymorphism of ERCC2 at codon 751 (OR=3.27; 95% CI=1.19-8.67; p&lt;0.05) and Asp/Asn at codon 312 (OR=2.14; 95% CI=1.03-4.29; p&lt;0.05) were significantly associated with a higher risk of developing bladder cancer. Again, Gln/Gln polymorphisms in bladder cancer (p&lt;0.05) were more likely to be present in individuals with cancer in the family.</div></div><div><h3>Conclusions</h3><div>This study reveals that susceptibility and bladder cancer aggressiveness are associated with polymorphisms at codon 751 and Asp/Asn at codon 312 of the ERCC2 gene.</div></div>","PeriodicalId":49225,"journal":{"name":"Cancer Genetics","volume":"288 ","pages":"Pages 126-132"},"PeriodicalIF":1.4,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142649458","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genetic profiling of metastatic colon adenocarcinoma in Iranian patients: Insights into pathogenic variants and tumor characteristics","authors":"Parnian Boroonsara ,&nbsp;Reza Jafarzadeh Esfehani ,&nbsp;Ali Taghizadeh Kermani ,&nbsp;Naeeme shakour","doi":"10.1016/j.cancergen.2024.11.003","DOIUrl":"10.1016/j.cancergen.2024.11.003","url":null,"abstract":"<div><h3>Introduction</h3><div>Colorectal cancer (CRC) remains one of the leading causes of cancer-related mortality, and understanding the genetic landscape is crucial for improving targeted therapies. This study aimed to analyze the tumor's genetic profiles of patients with metastatic CRC, focusing on pathogenic or likely pathogenic variants in tumor related genes.</div></div><div><h3>Materials and Methods</h3><div>The present cross-sectional study was conducted on 40 Persian patients with metastatic colorectal adenocarcinoma. Formalin-fixed paraffin-embedded tumor samples were analyzed using next generation sequencing technique to detect pathogenic variants. The patients' tumor characteristics, including differentiation grades and tumor sites (colon, rectum, or rectosigmoid), were documented and the relationship between variants and tumor characteristics was evaluated.</div></div><div><h3>Results</h3><div>The study population had a mean age of 55.75 ± 12.88 years, and 60 % were female. The most common tumor site was the colon (52.5 %), followed by rectosigmoid (27.5 %) and cecum (20 %). <em>APC</em> gene variants were prevalent in 72.5 % of patients, with the p.Arg876* variant being the most frequent. <em>TP53</em> gene variants were present in 65 %, with p.Trp146* and p.Arg273His being the most common. Pathogenic <em>KRAS</em> gene variants were observed in 50 %, significantly associated with rectosigmoid involvement (<em>p</em> = 0.001). The <em>ERBB2</em> CNVs were found in 25 % of patients and were associated with colon involvement (<em>p</em> = 0.021).</div></div><div><h3>Conclusion</h3><div>The study highlights the genetic diversity in Persian patients with metastatic colon adenocarcinoma and demonstrated that <em>APC</em> and TP53 variants were the most prevalent, while <em>KRAS</em> and <em>ERBB2</em> variants were associated with specific tumor sites. These findings provide a basis for personalized treatment strategies in CRC among Persian population.</div></div>","PeriodicalId":49225,"journal":{"name":"Cancer Genetics","volume":"288 ","pages":"Pages 133-136"},"PeriodicalIF":1.4,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142683193","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Recurrent cytogenetic abnormalities reveal alterations that promote progression and transformation in myelodysplastic syndrome","authors":"Rolando García,&nbsp;Tasnim Alkayyali,&nbsp;Luis Mosquera Gomez,&nbsp;Carter Wright,&nbsp;Weina Chen,&nbsp;Dwight Oliver,&nbsp;Prasad Koduru","doi":"10.1016/j.cancergen.2024.10.002","DOIUrl":"10.1016/j.cancergen.2024.10.002","url":null,"abstract":"<div><h3>Objective</h3><div>To illustrate patterns of cytogenetic abnormalities that promote progression and/or transformation in myelodysplastic syndrome.</div></div><div><h3>Methods</h3><div>In this study we evaluated three different data sets to identify recurrent cytogenetic abnormalities (RCAs) to delineate the cytogenetic evolutionary trajectories and their clinical significance.</div></div><div><h3>Results</h3><div>Datasets 1 and 2 were 2402 cross sectional samples from Mitelman database of Chromosome Aberrations and Gene Fusions in Cancer; these were used to discover RCAs and to validate them. Dataset 3 was a cohort of 163 institutional patients with serial samples from 35 % of them. This was used to further validate RCAs identified in the cross-sectional data, and their clinical impact. We identified MDS subtype associated RCAs, and some exclusive RCAs (Xp-, 2q-, 17q-, 21q-) that led to disease progression or transformation to leukemia. Evolutionary pathway analysis had shown temporal acquisition of RCAs. Therefore, presence of two or more RCAs suggests cooperative or complementary role in disease progression or transformation. Patients with one or more of these RCAs had poor prognosis and high risk for transformation. Genes frequently altered in MDS are mapped to some of the RCAs and suggest a close correlation between RCAs and molecular alterations in MDS. Karyotypic complexity, clonal evolution, loss of 17p had poor clinical outcomes.</div></div><div><h3>Conclusion</h3><div>This study identified a unique combination of RCAs that are components in distinct cytogenetic trajectories. Some of these were primary changes while others were secondary or tertiary changes. Acquiring specific additional aberrations predicts progression or transformation to leukemia.</div></div>","PeriodicalId":49225,"journal":{"name":"Cancer Genetics","volume":"288 ","pages":"Pages 92-105"},"PeriodicalIF":1.4,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142578229","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Potential use of SCAT1, SCAT2, and SCAT8 as diagnostic and prognosis markers in colorectal cancer","authors":"Parnia Mohammadi ,&nbsp;Shaghayegh Mohammadi ,&nbsp;Alireza Eghbalian ,&nbsp;Ali Jafari Meyabadi ,&nbsp;Mohammadreza Alizadeh ,&nbsp;Sina Taefehshokr","doi":"10.1016/j.cancergen.2024.10.004","DOIUrl":"10.1016/j.cancergen.2024.10.004","url":null,"abstract":"<div><div>Colorectal cancer (CRC) is the third most common malignancy and the second leading cause of cancer-related deaths worldwide. Despite advancements, the underlying mechanisms controlling CRC's etiology remain unclear, and reliable biomarkers for diagnosis and treatment are still lacking. Long noncoding RNAs (lncRNAs) are increasingly recognized for their role in cancer progression, though many remain unidentified and their functions poorly understood. In this study, we investigated the expression of SCAT1, SCAT2, and SCAT8 lncRNAs in both cancerous and adjacent non-cancerous tissues from CRC patients. Using cDNA synthesized from total RNA extracted from 100 tissue samples, we performed Real-Time PCR to measure the expression levels of these lncRNAs. In addition, their diagnostic potential was evaluated through ROC curve analysis. Our results demonstrate that SCAT1, SCAT2, and SCAT8 are significantly upregulated in CRC tissues, with ROC analysis suggesting SCAT1 as a moderate biomarker and SCAT2 and SCAT8 as promising biomarkers for CRC diagnosis. Moreover, we found strong correlations between SCAT1 and SCAT8, as well as SCAT2 and SCAT8. Collectively, our findings indicate that SCAT1, SCAT2, and SCAT8 may act as oncogenes in CRC, offering potential as novel biomarkers for diagnosis and prognosis.</div></div>","PeriodicalId":49225,"journal":{"name":"Cancer Genetics","volume":"288 ","pages":"Pages 106-109"},"PeriodicalIF":1.4,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142578230","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identification and characterization of ADAR1 mutations and changes in gene expression in human cancers","authors":"Anna Valentine ,&nbsp;Korey Bosart ,&nbsp;Wesley Bush ,&nbsp;Renee A. Bouley ,&nbsp;Ruben C. Petreaca","doi":"10.1016/j.cancergen.2024.10.007","DOIUrl":"10.1016/j.cancergen.2024.10.007","url":null,"abstract":"<div><div>ADAR1 (Adenosine deaminase action on RNA1) is involved in post-transcriptional RNA editing. ADAR1 mutations have been identified in many cancers but its role in tumor formation is still not well understood. Here we used available cancer genomes deposited on CSOMIC and cBioPortal to identify and characterize mutations and changes in ADAR1 expression in cancer cells. We identify several high frequency substitutions including one at R767 which is located in one of the dsRNA interacting domains. <em>In silico</em> protein structure analysis suggest the R767 mutations affect the protein stability and are likely to destabilize interaction with dsRNA. Gene expression analysis shows that in samples with under-expressed ADAR1, there is a statistically significant increase in expression of BLCAP (Bladder Cancer Associated Protein). Although BLCAP was initially identified in bladder cancers, more recent evidence shows that it is a tumor suppressor and BLCAP mutations have been detected in many cancer cells. Epistatic analysis using the cBioPortal mutual exclusivity calculator for the TCGA pan-cancer data shows that co-mutations between ADAR1 and other genes regulated by it are likely in cancer cells except for PTEN, AKT1 and BLCAP. This suggests that when ADAR1 function is impaired, PTEN, AKT1 and BLCAP become essential for survival of cancer cells. We also identified several samples with high mutation burden between ADAR1 and other genes regulated primarily in endometrial cancers. Finally, we show that the deaminase domain is highly conserved in metazoans and mutations within conserved residues do occur in human cancers suggesting that destabilization of the enzyme function is contributing to cancer development.</div></div>","PeriodicalId":49225,"journal":{"name":"Cancer Genetics","volume":"288 ","pages":"Pages 82-91"},"PeriodicalIF":1.4,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142570137","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Elucidating the prognostic and therapeutic significance of TOP2A in various malignancies","authors":"Guangchao Liu ,&nbsp;Wenlong Lin ,&nbsp;Kaifeng Zhang ,&nbsp;Kangxu Chen ,&nbsp;Guanglin Niu ,&nbsp;Yonghao Zhu ,&nbsp;Yixuan Liu ,&nbsp;Pengkun Li ,&nbsp;Zhihao Li ,&nbsp;Yang An","doi":"10.1016/j.cancergen.2024.10.005","DOIUrl":"10.1016/j.cancergen.2024.10.005","url":null,"abstract":"<div><div>Topoisomerase IIα (TOP2A) is a crucial enzyme that plays a vital role in DNA replication and transcription mechanisms. Dysregulated expression of TOP2A has been associated with various malignancies, including hepatocellular carcinoma, prostate cancer, colon cancer, lung cancer and breast cancer. In this review, we summarized the prognostic relevances of TOP2A in various types of cancer. The increased expression of TOP2A has been linked to resistance to therapy and reduced survival rates. Therefore, evaluating TOP2A levels could assist in identifying patients who may derive advantages from molecular targeted therapy. The amplification of <em>TOP2A</em> has been linked to a positive response to chemotherapy regimens that contain anthracycline. Nevertheless, the overexpression of TOP2A also indicates a heightened likelihood of disease recurrence and unfavorable prognosis. The prognostic significance of TOP2A has been extensively studied in various types of cancer. The increased expression of TOP2A is associated with poor clinical outcomes, indicating its potential as a valuable biomarker for assessing risk and stratifying treatment in these malignancies. However, further investigation is needed to elucidate the underlying mechanisms by which TOP2A influences cancer progression and to explore its potential as a therapeutic target.</div></div>","PeriodicalId":49225,"journal":{"name":"Cancer Genetics","volume":"288 ","pages":"Pages 68-81"},"PeriodicalIF":1.4,"publicationDate":"2024-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142511443","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Influence of polymorphisms on the phenotype of TLR1, TLR4 and TLR9 genes and their association with cervical cancer: Bioinformatics prediction analysis and a case-control study","authors":"Edilson Leite de Moura ,&nbsp;Israel Faustino dos Santos ,&nbsp;Paulo Pedro de Freitas ,&nbsp;Denise Macedo da Silva ,&nbsp;Ana Caroline Melo dos Santos ,&nbsp;Aline Cristine Pereira e Silva ,&nbsp;Abel Barbosa Lira Neto ,&nbsp;Rubens Pessoa de Barros ,&nbsp;Jhonatan David Santos das Neves ,&nbsp;Nirliane Ribeiro Barbosa ,&nbsp;Carolinne de Sales Marques ,&nbsp;Carlos Alberto de Carvalho Fraga ,&nbsp;Karol Fireman de Farias ,&nbsp;Elaine Virginia Martins de Souza Figueiredo","doi":"10.1016/j.cancergen.2024.10.001","DOIUrl":"10.1016/j.cancergen.2024.10.001","url":null,"abstract":"<div><div>Susceptibility to cervical cancer has been associated with Toll-like receptors (TLRs), which is an important component of innate immunity. According to previous studies, polymorphisms in TLRs genes can affect immune response pathways and lead to the development of cervical cancer. The present study aims to evaluate the functionality of polymorphisms in <em>TLR1, TLR4</em> and <em>TLR9</em> genes and their associations with cervical cancer. To identify the functionality of polymorphisms, we used the following tools: MUpro, ChimeraX, SNP2TFBS and GTEx. A case-control study including 57 cases (11 High-grade Intraepithelial Lesion - HSIL and 46 cervical cancer) and 67 clinically healthy controls was conducted in the Brazilian population. Polymorphisms genotyping was performed by real-time PCR, using TaqMan probes, using the allelic discrimination method. Bioinformatics prediction showed that the <em>TLR1</em> rs4833095 [NM_003263.4 (TLR1):c.743T&gt;C (p.Asn248Ser)] and <em>TLR4</em> rs4986790 [NM_138554.5 (TLR4):c.896A&gt;G (p.Asp299Gly)] polymorphisms alter the structure and stability of their respective proteins. <em>TLR9</em> rs187084 [NM_017442.3(TLR9):c.-1486A&gt;G] polymorphism seems to affect the THAP1 binding site and modify gene expression. In the case-control study, the c.743TC heterozygous genotype of the rs4833095 SNP in the <em>TLR1</em> gene was associated with an increased risk for HSIL/cervical cancer. No association of <em>TLR4</em> rs4986790 and <em>TLR9</em> rs187084 SNPs with HSIL/cervical cancer was found in the studied population. Allelic combination CAG (rs4833095/ rs4986790/ rs187084) increased the risk of cervical cancer. In conclusion, the present study identified that polymorphisms in <em>TLRs</em> genes can affect the phenotype of their respective genes and contribute to the development of HSIL or cervical cancer.</div></div>","PeriodicalId":49225,"journal":{"name":"Cancer Genetics","volume":"288 ","pages":""},"PeriodicalIF":1.4,"publicationDate":"2024-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142442238","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dysregulation of metallothionein MT1 sub-types in TCF3::PBX1 pre-B-cell acute lymphoblastic leukemia","authors":"Aditi Agnihotri,&nbsp;Vinesh S. Kamble,&nbsp;Satyajeet P. Khare","doi":"10.1016/j.cancergen.2024.09.003","DOIUrl":"10.1016/j.cancergen.2024.09.003","url":null,"abstract":"<div><p>The translocation between chromosomes 1 and 19 t(1;19) produces the TCF3::PBX1 fusion protein, which leads to childhood pre-B-cell acute lymphoblastic leukemia (ALL). The molecular mechanism of oncogenesis, however, remains obscure. This study aims to identify the genes specifically dysregulated in <em>TCF3</em>::<em>PBX1</em> translocation. The publicly available expression microarray datasets on ALL were used for weighted gene co-expression network analysis (WGCNA) to identify modules associated with TCF3::PBX1. The available knockdown and ChIP-Seq datasets were used to assess the direct targets of TCF3::PBX1. The WGCNA revealed a module enriched in genes involved in the metal ion stress to be positively correlated with <em>TCF3</em>::<em>PBX1,</em> with metallothionein isoform MT1 subtypes <em>MT1E, MT1F, MT1G, MT1H</em>, and <em>MT1X</em> as the hub genes. Of the 145 positively correlated genes, 19 were downregulated upon <em>TCF3</em>::<em>PBX1</em> knockdown. Eleven of these 19 genes including <em>MT1G</em>, showed TCF3::PBX1 occupancy at the promoter. The Metallothionein 1 family has been implicated in various cancers; however, their role in t(1;19) pre-B-cell ALL has not been previously demonstrated. Our analysis effectively accounts for the cellular and population-level heterogeneity and identifies a novel mechanism for the TCF3::PBX1 action.</p></div>","PeriodicalId":49225,"journal":{"name":"Cancer Genetics","volume":"288 ","pages":"Pages 54-58"},"PeriodicalIF":1.4,"publicationDate":"2024-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2210776224001248/pdfft?md5=de44d4c531ccf5f8fcf20354633b144d&pid=1-s2.0-S2210776224001248-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142272563","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Data-mining-based biomarker evaluation and experimental validation of SHTN1 for bladder cancer","authors":"Yueying Wang ,&nbsp;Jiajun Wang ,&nbsp;Tao Zeng ,&nbsp;Jiping Qi","doi":"10.1016/j.cancergen.2024.09.002","DOIUrl":"10.1016/j.cancergen.2024.09.002","url":null,"abstract":"<div><h3>Background</h3><p>Gene therapy in bladder cancer (BLCA) remains an area ripe for exploration. Recent studies have highlighted the crucial role of SHTN1 in the initiation and progression of various cancers and SHTN1 may have interacted with the FGFR gene. However, its specific function in BLCA remains unclear.</p></div><div><h3>Materials and methods</h3><p>We investigated the association between SHTN1 expression and prognosis, immune infiltration, and the tumor microenvironment (TME) across multiple malignancies using 433 BLCA samples from The Cancer Genome Atlas (TCGA). Differential gene expression analysis, functional annotation via Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Gene Set Enrichment Analysis (GSEA) were performed for SHTN1-related genes by using R packages. Immune response and TME scores, along with drug sensitivity profiles of SHTN1, were analyzed using R packages. Immunohistochemistry (IHC) and western blotting were conducted to assess SHTN1 expression in surgical specimens from BLCA patients.CCK8 assay and cells wound healing assay were performed.The bioinformatics was analyzed by R software. Significant differences were evaluated using unpaired t test.</p></div><div><h3>Results</h3><p>SHTN1 expression levels were significantly elevated in BLCA associated with poor prognosis (<em>p</em> &lt; 0.01). Receiver operating characteristic (ROC) curves and nomograms demonstrated the diagnostic and prognostic efficacy of SHTN1 in BLCA. Notably, SHTN1 expression was higher in high-grade BLCA compared to lower-grade (<em>p</em> = 5.6e-10), a finding corroborated by IHC and western blotting. Pathway enrichment analysis revealed significant involvement of the Neuroactive ligand-receptor interaction and Chemical carcinogenesis - DNA adducts signaling pathways among SHTN1 differentially expressed genes. In terms of immune infiltration, T cells CD8, T cells follicular helper, and dendritic cells were predominant in the SHTN1 low-expression group, whereas macrophages M0 and M2, and mast cells were predominant in the high-expression group. Multivariate Cox regression analysis identified SHTN1 as an independent prognostic factor for overall survival (HR = 2.93; 95 % CI = 1.40–6.13; <em>p</em> = 0.004).CCK8 and wound healing experiments showed that SHTN1 knockdown reduced the cell proliferation and migration. Western blot showed that the EMT pathway was clearly associated with SHTN1.</p></div><div><h3>Conclusions</h3><p>Our findings suggest that SHTN1 holds promise as a prognostic and diagnostic biomarker for BLCA. Moreover, it is closely associated with elevated immune infiltration and distinct characteristics of the tumor microenvironment in BLCA.</p></div>","PeriodicalId":49225,"journal":{"name":"Cancer Genetics","volume":"288 ","pages":"Pages 43-53"},"PeriodicalIF":1.4,"publicationDate":"2024-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2210776224001236/pdfft?md5=ae35bffa6f4d926b794617244bff8172&pid=1-s2.0-S2210776224001236-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142164277","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Novel ABL1 mutation in a Moroccan CML patient with Imatinib resistance","authors":"Ihssane El Bouchikhi ,&nbsp;Hajar Azami Idrissi ,&nbsp;Ahmed Lazraq ,&nbsp;Badreddine El Makhzen ,&nbsp;Mohamed Ahakoud ,&nbsp;Rhizlane Berrady ,&nbsp;Karim Ouldim ,&nbsp;Laila Bouguenouch ,&nbsp;Mohammed El-Azami-El-Idrissi","doi":"10.1016/j.cancergen.2024.08.083","DOIUrl":"10.1016/j.cancergen.2024.08.083","url":null,"abstract":"<div><p>Tyrosine Kinase Inhibitors (TKI), such as Imatinib, are known for their effectiveness in achieving complete remission from Chronic Myeloid Leukemia (CML), a malignancy caused by a reciprocal translocation between the terminal fragments of the long arms of chromosomes 9 and 22 that leads to the famous chimeric <em>BCR::ABL1</em> gene. Mutations in this fusion gene may induce resistance to TKI treatment, which requires prescribing a second-, or third-generation TKI medication. We report here a case of a Moroccan CML patient with secondary resistance to the frontline TKI treatment (Imatinib), in which, <em>BCR::ABL1</em> cDNA sequencing reveals the novel mutation p.K375M at the ABL1 Kinase Domain. <em>In-silico</em> prediction tools confirm the pathogenicity of the p.K375M substitution. Homology analysis indicated that the residue is highly conserved and located in a stable region. This potentially pathogenic mutation is likely to disrupt the BCR::ABL1-Imatinib binding, leading to the observed resistance. To overcome the treatment resistance, Imatinib should be substituted with a second-generation TKI medication, such as Dasatinib, Bosutinib, or Nilotinib. The present study further widens the spectrum of TKI resistance mutations and emphasizes particularly the crucial role of molecular investigation in personalizing treatment for CML patients, ensuring efficient follow-up and appropriate healthcare.</p></div>","PeriodicalId":49225,"journal":{"name":"Cancer Genetics","volume":"288 ","pages":"Pages 40-42"},"PeriodicalIF":1.4,"publicationDate":"2024-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2210776224001212/pdfft?md5=515d92531ddb4cb6b850a8860412204b&pid=1-s2.0-S2210776224001212-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142149078","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}