Cancer Genetics最新文献

{"title":"Data-mining-based biomarker evaluation and experimental validation of SHTN1 for bladder cancer","authors":"","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":null,"pages":null},"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":"","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":null,"pages":null},"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}

{"title":"Updates on liquid biopsies in neuroblastoma for treatment response, relapse and recurrence assessment","authors":"","doi":"10.1016/j.cancergen.2024.09.001","DOIUrl":"10.1016/j.cancergen.2024.09.001","url":null,"abstract":"<div><p>Neuroblastoma is a paediatric malignancy of the sympathoadrenal or Schwann cells derived from the neural crest. Risk stratification in neuroblastoma is informed by MYCN amplification, age, stage, ploidy, and segmental chromosomal alterations. High-risk cases bear dismal overall survival. A panel of pathology and imaging modalities are utilised for diagnosis, while treatment strategies depend on the risk group. Despite this, relapse can occur in 50% of high-risk neuroblastoma patients in remission post-treatment. Liquid biopsies typically comprise the sampling of the peripheral blood and are attractive since they are less invasive than surgical tumour tissue biopsies. Liquid biopsies retrieve circulating tumour DNA and circulating tumour RNA released by tumours in addition to circulating tumour cells. These biological materials can be utilised to analyse tumour genetic alterations. Monitoring tumour-derived molecular information can assist diagnostics, targeted therapy selection, and treatment while reflecting minimal residual disease, relapse, and recurrence. This study aims to review the latest research on liquid biopsies for disease diagnosis, assessing treatment efficacy, minimal residual disease, relapse, and recurrence in neuroblastoma. A deeper understanding of the application of liquid biopsies could inform future prospective clinical trials, and in time, facilitate their routine implementation in clinical practice.</p></div>","PeriodicalId":49225,"journal":{"name":"Cancer Genetics","volume":null,"pages":null},"PeriodicalIF":1.4,"publicationDate":"2024-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2210776224001224/pdfft?md5=dab4fb1d2596e6257a5b64de3f226b7e&pid=1-s2.0-S2210776224001224-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142146655","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":"BMS345541 is predicted as a repurposed drug for the treatment of TMZ-resistant Glioblastoma using target gene expression and virtual drug screening","authors":"","doi":"10.1016/j.cancergen.2024.08.082","DOIUrl":"10.1016/j.cancergen.2024.08.082","url":null,"abstract":"<div><p>Glioblastoma (GBM) is one of the most aggressive and fatal cancers, for which Temozolomide (TMZ) chemo drug is commonly used for its treatment. However, patients gradually develop resistance to this drug, leading to tumor relapse. In our previous study, we have identified lncRNAs that regulate chemoresistance through the competing endogenous RNA (ceRNA) mechanism. In this study, we tried to find FDA-approved drugs against the target proteins of these ceRNA networks through drug repurposing using differential gene expression profiles, which could be used to nullify the effect of lncRNAs and promote the sensitivity of TMZ in GBM. We performed molecular docking and simulation studies of predicted repurposed drugs and their targets. Among the predicted repurposed drugs, we found BMS345541 has a higher binding affinity towards its target protein - FOXG1, making it a more stable complex with FOXG1-DNA. The ADMET analysis of this drug BMS345541 shows a higher half-life and lower cytotoxicity level than other predicted repurposed drugs. Hence, we conjecture that this could be a better drug for increasing the sensitivity of TMZ for treating GBM patients.</p></div>","PeriodicalId":49225,"journal":{"name":"Cancer Genetics","volume":null,"pages":null},"PeriodicalIF":1.4,"publicationDate":"2024-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142099487","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":"Germline variant profiling of CHEK2 sequencing variants in breast cancer patients","authors":"","doi":"10.1016/j.cancergen.2024.08.081","DOIUrl":"10.1016/j.cancergen.2024.08.081","url":null,"abstract":"<div><p>The cell cycle checkpoint kinase 2 (<em>CHEK2</em>) is a tumor suppressor gene coding for a protein kinase with a role in the cell cycle and DNA repair pathways. Variants within <em>CHEK2</em> are associated with an increased risk of developing breast, colorectal, prostate and several other types of cancer. Comprehensive genetic risk assessment leads to early detection of hereditary cancer and provides an opportunity for better survival. Multigene panel screening can identify the presence of pathogenic variants in hereditary cancer predisposition genes (HCPG), including <em>CHEK2</em>. Multigene panels, however, also result in large quantities of genetic data some of which cannot be interpreted and are classified as variants of uncertain significance (VUS). A VUS provides no information for use in medical management and leads to ambiguity in genetic counseling. In the absence of variant segregation data, in vitro functional analyses can be used to clarify variant annotations, aiding in accurate clinical management of patient risk and treatment plans. In this study, we performed whole exome sequencing (WES) to investigate the prevalence of germline variants in 210 breast cancer (BC) patients and conspicuously among the many variants in HCPGs that we found, we identified 16 individuals with non-synonymous or frameshift <em>CHEK2</em> variants, sometimes along with additional variants within other BC susceptibility genes. Using this data, we investigated the prevalence of these <em>CHEK2</em> variants in African American (AA) and Caucasian (CA) populations identifying the presence of two novel frameshift variants, c.1350delA (p.Val451Serfs*18) and c.1528delC (p.Gln510Argfs*3) and a novel missense variant, c262C&gt;T (p.Pro88Ser). Along with the current clinical classifications, we assembled available experimental data and computational predictions of function for these <em>CHEK2</em> variants, as well as explored the role these variants may play in polygenic risk assessment.</p></div>","PeriodicalId":49225,"journal":{"name":"Cancer Genetics","volume":null,"pages":null},"PeriodicalIF":1.4,"publicationDate":"2024-08-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142087053","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":"Brain abscesses, neutropenia, and B-ALL: Multiple testing modalities required to confirm PDCD10 and ETV6 dual diagnoses","authors":"","doi":"10.1016/j.cancergen.2024.08.001","DOIUrl":"10.1016/j.cancergen.2024.08.001","url":null,"abstract":"<div><p>Recognition of patients with multiple diagnoses, and the unique challenges they pose to clinicians and laboratorians, is increasing rapidly as genome-wide genetic testing grows in prevalence. We describe a unique patient with dual diagnoses of <em>PDCD10</em>-related cerebral cavernous malformations and <em>ETV6</em>-related thrombocytopenia with associated neutropenia. She presented with brain abscesses as an infant, which is highly atypical for these disorders in isolation. Confirming her diagnoses depended on thorough phenotyping both during and after her acute illness. Furthermore, the causative variant in <em>ETV6</em> is a novel single-exon deletion that required multiple modalities with manual review to confirm, including unique use of polymorphic nucleotides in trio exome data. She illustrates the special challenges of patients with multiple diagnoses, and the multiple tools clinicians and laboratorians must use to treat them.</p></div>","PeriodicalId":49225,"journal":{"name":"Cancer Genetics","volume":null,"pages":null},"PeriodicalIF":1.4,"publicationDate":"2024-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142044372","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":"Focal cortical dysplasia type IIIb associated with a KRAS-mutant ganglioglioma","authors":"","doi":"10.1016/j.cancergen.2024.07.004","DOIUrl":"10.1016/j.cancergen.2024.07.004","url":null,"abstract":"","PeriodicalId":49225,"journal":{"name":"Cancer Genetics","volume":null,"pages":null},"PeriodicalIF":1.4,"publicationDate":"2024-08-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141984898","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":"A complex t(15;22;17)(q22;q11.2;q21) variant of APL","authors":"","doi":"10.1016/j.cancergen.2024.07.003","DOIUrl":"10.1016/j.cancergen.2024.07.003","url":null,"abstract":"<div><p>The present study described an extremely rare case of acute promyelocytic leukemia (APL) characterized by a complex three‑way (15;22;17)(q22;q11.2;q21) translocation. Acute promyelocytic leukemia (APL) is a specific subtype of acute myeloid leukemia with distinctive clinical and therapeutic characteristics. Besides being characterized by the t(15;17)(q22;q12) translocation, this subtype is also notable for its response to all-trans-retinoic acid (ATRA) treatment. APL is highly responsive to a combination of ATRA and chemotherapeutic agents, achieving over 90 % complete remission rates and over 80 % long-term remission rates. In this case, a 79-year-old male patient presented with complaints of weakness, fatigue, and petechial rash, with no other significant medical history except for diabetes mellitus and hypertension. Conventional cytogenetic methods, dual-color dual-fusion, and dual-color break-apart fluorescent in situ hybridization techniques together identified the t(15;22;17) translocation. RT-PCR analysis was performed for expression of PML/RARA fusion transcripts. The patient, diagnosed with APL, exhibited a complete response to all-trans retinoic acid (ATRA) and idarubicin treatment. In this paper, we present the second documented case of t(15;22;17) and explore the remarkable remission observed following treatment with All-Trans Retinoic Acid (ATRA).</p></div>","PeriodicalId":49225,"journal":{"name":"Cancer Genetics","volume":null,"pages":null},"PeriodicalIF":1.4,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141839783","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":"Whole genome joint analysis reveals ATM:C.1564_1565del variant segregating with Ataxia-Telangiectasia and breast cancer","authors":"","doi":"10.1016/j.cancergen.2024.07.002","DOIUrl":"10.1016/j.cancergen.2024.07.002","url":null,"abstract":"<div><p><em>ATM</em> gene is implicated in the development of breast cancer in the heterozygous state, and Ataxia-telangiectasia (A-T) in a homozygous or compound heterozygous state. Ataxia-telangiectasia (A-T) is a rare cerebellar ataxia syndrome presenting with progressive neurologic impairment, telangiectasia, and an increased risk of leukemia and lymphoma.</p><p>Although the role of <em>ATM,</em> separately, in association with A-T and breast cancer is well documented, there is a limited number of studies investigating <em>ATM</em> variants when segregating with both phenotypes in the same family. Here, using joint analysis and whole genome sequencing, we investigated <em>ATM</em> c.1564_1565del in a family with one homozygous member presenting with A-T (OMIM # <span><span>208900</span><svg><path></path></svg></span>) and three heterozygous members, of whom one had breast cancer (OMIM #<span><span>114480</span><svg><path></path></svg></span>). To our knowledge, this is the first study of <em>ATM</em> c.1564_1565del segregation with both A-T and breast cancer phenotypes within the same kindred. This study highlights the need for a comprehensive genomic approach in the appropriate cancer risk management of heterozygote carriers of <em>ATM</em> in families with A-T.</p></div>","PeriodicalId":49225,"journal":{"name":"Cancer Genetics","volume":null,"pages":null},"PeriodicalIF":1.4,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141789616","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":"A mechanistic insight into cancer progression mediated by Nucleoporins","authors":"","doi":"10.1016/j.cancergen.2024.07.001","DOIUrl":"10.1016/j.cancergen.2024.07.001","url":null,"abstract":"<div><p>The nuclear pore complexes are essential for cellular and molecular processes such as trafficking between the cytoplasm and the nucleus, chromatin, transcriptional outputs, and DNA damage repair. Nucleoporins, components of nuclear pore complexes, have been linked to cancer through nucleo-cytoplasmic cargo trafficking, cell division, signalling pathways, chromatin-related processes, and protein stability and degradation. This study aims to understand how nucleoporins specifically contribute to cancer proliferation and progression across various cancer types. Accordingly, angles such as nuclear trafficking, fusion proteins, tumour suppressors, signalling pathways, tumour microenvironment, nucleosomes, and chromatin processes were found to bridge the function of nucleoporins and cancer progression, and the underlying mechanisms have been analysed in this study. A deep understanding of the function of nucleoporins in cancer progression will pave the way for the effective targeting of these molecules for therapeutic gain. Improved treatment responses can enhance the quality of life of cancer patients.</p></div>","PeriodicalId":49225,"journal":{"name":"Cancer Genetics","volume":null,"pages":null},"PeriodicalIF":1.4,"publicationDate":"2024-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2210776224000279/pdfft?md5=92d61fc34322f28f90c92d08e9204157&pid=1-s2.0-S2210776224000279-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141636865","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}