Cancer Genetics最新文献

{"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}

{"title":"Updates on liquid biopsies in neuroblastoma for treatment response, relapse and recurrence assessment","authors":"Leila Jahangiri","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":"288 ","pages":"Pages 32-39"},"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":"Rojalin Nayak,&nbsp;Bibekanand Mallick","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":"288 ","pages":"Pages 20-31"},"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":"Claire McCarthy-Leo ,&nbsp;Scott Baughan ,&nbsp;Hunter Dlugas ,&nbsp;Prisca Abraham ,&nbsp;Janice Gibbons ,&nbsp;Carolyn Baldwin ,&nbsp;Sarah Chung ,&nbsp;Gerald L. Feldman ,&nbsp;Gregory Dyson ,&nbsp;Russell L. Finley Jr. ,&nbsp;Michael A. Tainsky","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":"288 ","pages":"Pages 10-19"},"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}